Information on EC 1.4.1.3 - glutamate dehydrogenase [NAD(P)+]

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea

EC NUMBER
COMMENTARY
1.4.1.3
-
RECOMMENDED NAME
GeneOntology No.
glutamate dehydrogenase [NAD(P)+]
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
mechanism
-
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
alternative order mechanism at pH 9.5
-
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
kinetic data suggest either a rapid-equilibrium random mechanism or a compulsory mechanism with binding sequence NH4+, NAD(P)H, 2-oxoglutarate
dogfish
-
L-glutamate + H2O + NAD(P)+ = 2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
compulsory order mechanism at pH 8.8
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reductive amination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
-
Arginine and proline metabolism
-
-
D-Glutamine and D-glutamate metabolism
-
-
GABA shunt
-
-
glutamate and glutamine metabolism
-
-
L-glutamate biosynthesis II
-
-
L-glutamate degradation X
-
-
L-ornithine de novo biosynthesis
-
-
Metabolic pathways
-
-
Nitrogen metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
L-glutamate:NAD(P)+ oxidoreductase (deaminating)
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dehydrogenase, glutamate (nicotinamide adenine dinucleotide (phosphate))
-
-
-
-
GDH
-
-
-
-
glutamic acid dehydrogenase
-
-
-
-
glutamic dehydrogenase
-
-
-
-
L-glutamate dehydrogenase
-
-
-
-
L-glutamic acid dehydrogenase
-
-
-
-
Legdh1
-
-
-
-
Membrane protein 50
-
-
-
-
MP50
-
-
-
-
NAD(P)-glutamate dehydrogenase
-
-
-
-
NAD(P)H-dependent glutamate dehydrogenase
-
-
-
-
NAD(P)H-utilizing glutamate dehydrogenase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9029-12-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain PCI 219
-
-
Manually annotated by BRENDA team
Bacillus subtilis PCI 219
strain PCI 219
-
-
Manually annotated by BRENDA team
high activity-form and low-activity form
-
-
Manually annotated by BRENDA team
strictly anaerobic bacterium
-
-
Manually annotated by BRENDA team
brain isoenzymes 1 and 2, probably encoded by different genes
-
-
Manually annotated by BRENDA team
dogfish
-
-
-
Manually annotated by BRENDA team
glutamate dehydrogenase 1 and 2
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
gene GLUD2 encoding isozyme GDH2
SwissProt
Manually annotated by BRENDA team
two human isozymes hGDH1 and hGDH2, genes GLUD1 and GLUD2
-
-
Manually annotated by BRENDA team
super-ovulating C57BL6/SJL hybrid mice, gene GlUD1
UniProt
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
super-ovulating C57BL6/SJL hybrid mice, gene GlUD1
UniProt
Manually annotated by BRENDA team
sp. KOD1, hyperthermophilic archeon isolated from kodakara island, japan
-
-
Manually annotated by BRENDA team
ES4, hyperthermophilic archeon
-
-
Manually annotated by BRENDA team
precursor
UniProt
Manually annotated by BRENDA team
strain DSM 158
-
-
Manually annotated by BRENDA team
enhanced ammonium concentrations and a reduced carbon supply induce the enzyme activity
-
-
Manually annotated by BRENDA team
Sulfolobus solfataricus MT-4
-
SwissProt
Manually annotated by BRENDA team
membrane-bound enzyme exhibits microtubule-binding activity
-
-
Manually annotated by BRENDA team
strain HB27
-
-
Manually annotated by BRENDA team
GWE1, a Gram-positive microaerophilic microorganism isolated from from the interior of a sterilization drying oven
-
-
Manually annotated by BRENDA team
Richardson's ground squirrel
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
while GDH in most mammals is encoded by a single GLUD1 gene, humans and other primates have acquired a GLUD2 gene with distinct tissue expression profile
physiological function
-
influence of alcohol on leukocyte GLDH activity, its diagnostic value, influence on metabolism and cells toxicity is analysed. Examination is conducted in 238 alcoholics and in 244 healthy persons. A fast increase of leukocyte GLDH activity after break in alcohol consumption is found. After 24 hours, activity increases by 21.8% (median 31.6%), after seven days by 33% (median 52%), yet after a short interval since last alcohol intake (up to 48 hours), it increases by 32% (median 36%)
physiological function
P49448
the glutamate dehydrogenase catalyzes the reversible interconversion of glutamate to 2-oxoglutarate and ammonia using NADP(H) and NAD(H) as cofactors, thus interconnecting amino acid and carbohydrate metabolism. Mammalian GDH is allosterically regulated, with GTP and ADP being the main negative and positive modulators, respectively
physiological function
-
allosteric activation and inhibition is important for enzyme regulation, overview
physiological function
-
the enzyme provides a pathway for ammonium assimilation
physiological function
-
the enzyme provides a pathway for ammonium assimilation, although the activity for ammonium is low
metabolism
P10860
GDH1 is the protein partner for pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm). Facilitating the recycling of BCATm to form metabolon, GDH1 acts as a catalytic machine
additional information
P26443
transgenic mice overexpressing the enzyme in brain have decreases in MAP2A labeling of dendrites and in synaptophysin labeling of presynaptic terminals, increasing in neuronal numbers and dendrite and presynaptic terminal labeling with advancing age, and show decreases in long-term potentiation of synaptic activity and in spine density in dendrites of CA1 neurons. Despite overexpression of Glud1 in all neurons of the central nervous system, the Tg mice suffer neuronal losses in select brain regions, e.g., the CA1 but not the CA3 region, dendrite structure and neuronal numbers in brains of transgenic mice, overview. The transgenic mice are significantly more resistant than wild-type mice to induction and duration of anesthesia produced by anesthetics that suppress Glu neurotransmission, phenotype, overview
additional information
-
glutamate is bound to the active site of GdhB, the GdhB-Glu complex takes an open-like structure. No substrate is found in the active site of the GdhAGdhB-Leu complex, while six leucine molecules are found at the interfaces of three subunits
additional information
Mus musculus C57BL6/SJL hybrid
-
transgenic mice overexpressing the enzyme in brain have decreases in MAP2A labeling of dendrites and in synaptophysin labeling of presynaptic terminals, increasing in neuronal numbers and dendrite and presynaptic terminal labeling with advancing age, and show decreases in long-term potentiation of synaptic activity and in spine density in dendrites of CA1 neurons. Despite overexpression of Glud1 in all neurons of the central nervous system, the Tg mice suffer neuronal losses in select brain regions, e.g., the CA1 but not the CA3 region, dendrite structure and neuronal numbers in brains of transgenic mice, overview. The transgenic mice are significantly more resistant than wild-type mice to induction and duration of anesthesia produced by anesthetics that suppress Glu neurotransmission, phenotype, overview
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobutyrate + H2O + NADP+
2-oxobutyrate + NH3 + NADPH
show the reaction diagram
-
3% of activity with L-glutamate
-
?
2-oxoglutarate + NAD(P)H + NH3
L-glutamate + NAD(P)+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NAD(P)H + NH3
L-glutamate + NAD(P)+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
-
-
-
-
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
-
-
-
-
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
P00367
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
P49448
-
-
-
?
2-oxoglutarate + NADH + NH3
L-glutamate + NAD+ + H2O
show the reaction diagram
-
no activity with NAD+ as cofactor
-
-
ir
2-oxoglutarate + NADPH + NH3
L-glutamate + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
2-oxoglutarate + NADPH + NH3
L-glutamate + NADP+ + H2O
show the reaction diagram
-
-
-
-
r
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
show the reaction diagram
-
-
-
-
r
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
show the reaction diagram
-
-
-
-
-
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
show the reaction diagram
-
-
-
-
r
2-oxoglutarate + NH3 + NADH
L-glutamate + H2O + NAD+
show the reaction diagram
-
specific activity in the presence of NADH is about 30% of that with NADPH
-
-
r
2-oxoglutarate + NH3 + NADPH
L-glutamate + H2O + NADP+
show the reaction diagram
-
-
-
-
r
2-oxoglutarate + NH3 + NADPH + H+
L-glutamate + H2O + NADP+
show the reaction diagram
O59650
-
-
-
?
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
-
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
show the reaction diagram
-
very low activity
-
-
-
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
show the reaction diagram
-
very low activity
-
?
alanine + H2O + NAD(P)+
pyruvate + NH3 + NAD(P)H
show the reaction diagram
-
very low activity
-
-
-
homocysteinesulfinate + H2O + NAD(P)+
?
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + 2-azido-NAD+
2-oxoglutarate + NH3 + 2-azido-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + N6-(2-aminoethyl)-NAD(P)H
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-hydroxy-3-trimethylammoniumpropyl)-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + N6-(3-sulfonatopropyl)-NAD+
2-oxoglutarate + NH3 + N6-(2-sulfonatopropyl)-NADH
show the reaction diagram
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
dogfish
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
highly specific for 2-oxoglutarate and glutamate
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
highly specific for 2-oxoglutarate and glutamate
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
very low activity with: leucine, alpha-aminobutyrate, valine, isoleucine and methionine
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
rate of glutamate synthesis is several-fold higher than the rate for the reverse reaction
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
enzyme for the main route for ammonia assimilation at low concentrations of ammonia
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
Bacillus subtilis PCI 219
-
-
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
ir
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
P49448
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
P10860
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
P26443
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
Mus musculus C57BL6/SJL hybrid
P26443
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
ir
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
P49448
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
P10860
-
-
-
?
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
P26443
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
Mus musculus C57BL6/SJL hybrid
P26443
-
-
-
r
L-glutamate + H2O + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)+
2-oxoglutarate + NH3 + polyethylenglycol-N6-(2-aminoethyl)-NAD(P)H
show the reaction diagram
-
-
-
?
L-glutamate + NAD+ + H2O
2-oxoglutarate + NADH + NH3
show the reaction diagram
-
-
-
-
?
L-glutamate + NAD+ + H2O
2-oxoglutarate + NADH + NH3
show the reaction diagram
P10860
-
-
-
r
norvaline + H2O + NAD(P)+
2-oxopentanoate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
-
-
norvaline + H2O + NAD(P)+
2-oxopentanoate + NH3 + NAD(P)H
show the reaction diagram
-
-
-
-
?
norvaline + H2O + NADP+
2-oxovalerate + NH3 + NADPH
show the reaction diagram
-
activity is 20% of that observed in the presence of 2-oxoglutarate and L-glutamate
-
-
r
valine + H2O + NADP+
2-oxovalerate + NH3 + NADPH
show the reaction diagram
-
3% of activity with L-glutamate
-
?
L-glutamate + NADP+ + H2O
2-oxoglutarate + NADPH + NH3
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
the similarity in relative activation when both cofactors are present, combined with consistently greater GDH product formation from equimolar NADH than with NADPH, does not support the idea that there is a preferential utilization of NADPH by bovine GDH
-
-
-
additional information
?
-
-
no activity in the amination reaction direction with NADH or NADPH, 2-oxoglutarate and ammonia
-
-
-
additional information
?
-
-
the glutamate formation activity is 3fold higher than the glutamate deamination activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H
show the reaction diagram
-
enzyme for the main route for ammonia assimilation at low concentrations of ammonia
-
r
L-glutamate + H2O + NAD(P)+
2-oxoglutarate + NH3 + NAD(P)H + H+
show the reaction diagram
-
-
-
-
?
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
ir
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
P49448
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
P26443
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NAD+
2-oxoglutarate + NH3 + NADH + H+
show the reaction diagram
Mus musculus C57BL6/SJL hybrid
P26443
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
ir
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
P49448
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
P26443
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
-
-
-
-
r
L-glutamate + H2O + NADP+
2-oxoglutarate + NH3 + NADPH + H+
show the reaction diagram
Mus musculus C57BL6/SJL hybrid
P26443
-
-
-
r
additional information
?
-
-
the similarity in relative activation when both cofactors are present, combined with consistently greater GDH product formation from equimolar NADH than with NADPH, does not support the idea that there is a preferential utilization of NADPH by bovine GDH
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD(P)H
-
-
NAD+
-
-
NAD+
-
2 times higher reaction rate than with NADP+
NAD+
-
glutamate dehydrogenase 2 uses only NAD+ in the deamination direction
NAD+
-
-
NAD+
dogfish
-
-
NAD+
-
no activity with NADP+
NAD+
-
activity with NAD+ is 3-5fold higher than using NADP+
NAD+
P10860
utilizes NAD+ for nitrogen liberation
NAD+
P10860
GDH1 uses NAD+ or NADP+ as coenzyme
NAD+
P26443
-
NAD+
-
both NAD+ and NADP+ are utilized as cofactors. The inactive enzyme also binds cofactors
NADH
-
reaction rate NADH/NADPH: 6
NADH
-
-
NADH
-
reaction rate NADH/NADPH: 15
NADH
-
reaction rate NADH/NADPH: 1.3 (GDH1); reaction rate NADH/NADPH: 4.5 (GDH2)
NADH
-
preferred cofactor
NADH
-
ratio of NADH/NADPH-dependent activity: 1/1.6
NADH
P26443
-
NADP+
-
with NADP+ initial rates are much slower than with NAD+
NADP+
-
-
NADP+
-
only 5% of the activity with NAD+
NADP+
dogfish
-
-
NADP+
-
enzyme activity with NADP+ is higher than the activity with NAD+
NADP+
-
specific for
NADP+
-
no activity with NAD+
NADP+
-
lower activity with NADP+ compared to NAD+
NADP+
P10860
utilizes NADP+ for nitrogen incorporation
NADP+
P10860
GDH1 uses NAD+ or NADP+ as coenzyme
NADP+
P26443
-
NADP+
-
both NAD+ and NADP+ are utilized as cofactors. The inactive enzyme also binds cofactors
NADPH
-
reaction rate NADH/NADPH: 6
NADPH
-
-
NADPH
-
reaction rate NADH/NADPH: 15
NADPH
-
glutamate dehydrogenase 1, reaction rate NADH/NADPH: 1.3; glutamate dehydrogenase 2, reaction rate NADH/NADPH: 4.4
NADPH
-
NADPH/NADH ratio of reaction rate: 10/1, NAD+/NADH ratio of reaction rate: 5/1
NADPH
-
amination activity is 5fold higher with NADPH than that with NADH
NADPH
-
3fold higher activity than with NADH
NADPH
-
at lower maximal rate than with NADH
NADPH
P26443
-
2-Azido-NAD+
-
-
additional information
-
2 soybean isoenzymes with different coenzyme specificities, glutamate dehydrogenase 1: active with NADH, NAD+, NADPH and NADP+, glutamate dehydrogenase 2: active with NADH, NAD+, NADPH but not NADP+
-
additional information
-
cofactor not mentioned
-
additional information
-
the enzyme can use both NAD+ and NADP+ as electron acceptors, displaying more affinity for NADP+ than for NAD+. No activity with NADH or NADPH
-
additional information
-
GDH is a dual-cofactor GDH, with activity that is greater with NAD+/NADH than with NADP+/NADPH
-
additional information
-
GDH is a dual-cofactor GDH
-
additional information
-
the similarity in relative activation when both cofactors are present, combined with consistently greater GDH product formation from equimolar NADH than with NADPH, does not support the idea that there is a preferential utilization of NADPH by bovine GDH. In the reductive amination direction, the rates of product formation are always greater for NADH oxidation than NADPH oxidation
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
1 mM, 1.5fold activation of isozymes 1 and 3, 2.5fold activation of isozyme 2
KCl
-
3 mM, activates to 144% of control
NaCl
-
3 M, 67fold activation
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-Azido-NAD+
-
0.1 mM, 60% inhibition after 3 min of photolabeling
2-oxobutyrate
-
-
2-oxoglutarate
-
-
2-oxoglutarate
-
-
2-oxoglutarate
-
-
2-oxovalerate
-
-
4-iodoacetamidosalicylic acid
-
-
5-Bromofuroate
-
-
5-Chlorofuroate
-
-
5-Nitrofuroate
-
-
8-Azidoguanosine 5'-triphosphate
-
used for affinity photolabeling, 0.1 mM, 95% inhibition
ADP
-
above pH 7.0: allosteric activation, pH 6.0-7.0: strong inhibition
alanine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
AlCl3
-
increase in sensitivity to aluminium as pH decreases, inhibitory effect is predominant below pH 7.0, no effect above pH 8.5. Completely inactivated enzyme contains 2 mol of aluminum per mol of subunit. Citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or EDTA efficiently protects against inactivation. Citrate and NaF release aluminum from the completely inactivated aluminum-enzyme complex and fully recover enzyme activity. Binding of aluminum induces a decrease in alpha helices and beta sheets and an increase in random coil
alpha-Ketoglutarate oxime
-
-
alpha-Monofluoroglutarate
-
-
alpha-Tetrazole
-
-
Aminooxyacetate
-
5 mM, weak inhibition of isozymes 1-3
AMP
-
inhibits only NADPH-linked activity
ATP
-
1 mM, 65% inhibition of NADH reaction due to chelating properties of ATP
ATP
-
strong inhibition
ATP
-
-
ATP
-
membrane-bound enzyme form, inhibition of microtubule-binding activity
ATP
-
strong inhibition at 37C, no inhibition at 5C
ATP
-
wild-type: inhibition at 0.1 mM and between 0.5-1.0 mM and above, activation at 1 mM, H454Y and S448P mutant enzyme: activation between 0.1-1 mM, inhibition above, R463A mutant enzyme: progressive inhibition between 0.01 and 10 mM
ATP
-
0.01-0.1 mM
cardiolipin
-
-
Chloroquine
-
potent inhibitor of isozymes GDH1 and GDH2 at a dose-dependent manner, the inhibitory effect of chloroquine on GDH2 is abolished by the presence of ADP and L-leucine, whereas GTP does not change the sensitivity to chloroquine inhibition, shows a non-competitive inhibition against 2-oxoglutarate and an uncompetitive inhibition against NADH
citrate
-
10 mM, 60% inhibition of oxidative deamination
D-glutamate
-
10 mM, 57% inhibition of NADP+-linked activity, 30% inhibition of NADPH-linked activity
D-glutamate
-
2 mM, 11% inhibition, 6 mM, 34% inhibition
diethylstilbestrol
-
-
Ditetrazole
-
-
EDTA
-
complete loss of NADH and NAD+ activities, NADPH activity unaffected
EDTA
-
5 mM, 80-90% inhibition of isozymes 1-3
fumarate
-
-
gamma-Tetrazole
-
-
GDP
P10860
strong allosteric inhibitor of GDH1 leading to a 90% reduction of activity. Addition of increasing concentrations of pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm) leads to an increasing protection from GDP inhibition
glutamate
-
-
glutamate
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
Glutarate
-
-
Glutarate
-
shows no affinity for N6-linked NAD+ but is biospecifically adsorbed to S6-linked NAD+ derivatives in the presence of its soluble kinetic-based enzyme capture ligand glutarate
Glyoxal
-
-
Glyoxal
P10860
67% inhibition at 1 mM
GTP
-
inhibition at pH 9.0, activation in presence of electrolytes at pH 6.0
GTP
-
1 mM, 42% inhibition due to chelating properties of GTP
GTP
-
membrane-bound liver enzyme, complete inhibition
GTP
-
0.06 mM, 95% inhibition
GTP
-
strong inhibition at 37C, weak inhibition at 5C
GTP
-
little inhibition of H454Y mutant enzyme
GTP
-
inhibition of wild-type enzyme and mutant enzymes r470H and N498S. No inhibition of mutant enzyme G456A. IC50 of wild-type enzyme is 0.00019 mM, IC50 of mutant enzyme G456A is 0.0028 mM, IC50 of mutant enzyme R470G is 0.00017 mM, IC50 of mutant enzyme N498S is 0.0002 mM
GTP
-
inhibits wild-type enzyme and mutant enzyme E279G
GTP
-
IC50 for wild-type GLUD1: 0.0122 mM, IC50 for mutant enzyme R443S: 0.0162 mM, IC50 for mutant enzyme M415L: 0.0147 mM, IC50 for mutant enzyme M370L: 0.0113 mM, IC50 for mutant enzyme S331T: 0.0108 mM
GTP
P49448
potent inhibitor. IC50 for wild-type enzyme is 0.00019 mM, IC50 for mutant enzyme G456A is 0.0028 mM. ADP renders the GLUD1-derived enzyme less sensitive to GTP inhibition; totally insensitive to, it becomes amenable to GTP inhibition in presence of ADP
GTP
P10860
8.23% activity in the presence of 0.01 mM ATP
GTP
-
inhibits isozyme GDH1
GTP
-
GTP inhibition is attenuated to some extent by the proteolysis with TLCK-treated chymotrypsin
GTP
-
efective inhibitor: activity below 10% of its full activity; GDH2 is resistent to GTP inhibition
GTP
P49448
negative allosteric regulator
GTP
-
allosteric regulation, low inhibition of the deamination reaction and strong inhibition of the amination reaction
histidine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
imidodiacetic acid
-
-
Isophthalate
-
-
Isophthalate
-
competitive vs. glutamate
KCN
-
50 mM, strong inhibition of isozymes 1-3
L-aspartate
-
inhibition of NADPH linked reaction, activation of NAD(H) linked reaction
L-glutamate
-
-
lysine
-
weak inhibition at pH 8.5, strong inhibition at pH 10.0
m-Bromobenzoate
-
-
m-chlorobenzoate
-
-
m-Iodobenzoate
-
-
m-Nitrobenzoate
-
-
malate
-
5 mM, complete inhibition of NADH-linked activity
Methylacetimidate
-
100 mM, moderate inhibition of isozymes 1-3
N-(N'-acetyl-4-sulfamoylphenyl)maleimide
-
-
NaCl
-
100 mM, 50% inhibition of NADH and NAD+ dependent reactions
NaCl
-
-
NAD+
-
incubation with 0.1 mM for 60 min inhibits hGDH1 and hGDH2 by 75% and 70%, respectively, incubations for longer time periods up to 3 h, does not further increase the inhibition of hGDH isoenzymes, ADP-ribosylated hDGH isozymes are reactivated by Mg2+-dependent mitochondrial ADP-ribosylcysteine hydrolase
NADH
-
high concentration
NADP+
-
-
NADPH
-
-
NH4+
-
-
Ni2+
-
1 mM, moderate inhibition of isozymes 1-3
norvaline
-
-
o-phenanthroline
-
5 mM, strong inhibition of isozymes 1-3
o-phthalaldehyde
-
0.1 mM, 98% inhibition after 5 min at 60C, competitive vs. 2-oxoglutarate and NADH
oxaloacetate
-
5 mM, 79% inhibition of oxidative deamination
oxaloacetate
-
5 mM, 20-25% inhibition of NADH- and NAD+-dependent activities
oxalylglycine
-
competitive vs. 2-oxoglutarate, uncompetitive vs. NADPH, noncompetitive vs. NH4+
Oxydiglycolic acid
-
-
p-chloromercuribenzoic acid
-
progressive decrease in enzyme activity of both isoenzymes, inhibition is not affected by addition of GTP or ADP
p-hydroxymercuribenzoate
-
5 mM, moderate inhibition of isozymes 1-3
palmitoyl-CoA
-
-
palmitoyl-CoA
-
concentration-dependent inhibition, GDH1 is less sensitive to palmitoyl-CoA inhibition than GDH2
Phenylglyoxal
-
4 mM, 75% inhibition, uncompetitive vs. 2-oxoglutarate, noncompetitive vs. NADH
phosphate
-
pH 8.0-9.0: activation, pH 6.0-7.6: almost complete inhibition with 400 mM
phosphatidylserine
-
assumed to be a simple non-competitive inhibition
phosphoenolpyruvate
-
-
pyridoxal
-
NADH and NADPH protect from inactivation
pyridoxal 5'-phosphate
-
0.11 mM, approx. 30% inactivation after 10 min, 0.78 mM, 80% inactivation, inactivation is completely reversed by dialysis
pyridoxal 5'-phosphate
dogfish
-
NAD+ and NADP+ protect from inactivation in the presence of sodium glutarate
pyridoxal 5'-phosphate
-
2 mM, complete loss of activity
pyridoxal 5'-phosphate
-
5 mM, 100% inhibition
Sodium acetate
-
at 5C only
sodium dodecylsulfate
-
time-dependent irreversible inhibition, 0.2 mM, 37% inhibition, 0.15 mM, 50% inhibition after 30 min, in the presence of 2-oxoglutarate after 370 min
succinate
-
5 mM, complete inhibition of NADH-linked activity
sulfite
-
uncompetitive
Thiodiglycolic acid
-
-
Zn2+
-
1 mM, strong inhibition of isozymes 1-3
methylglyoxal
P10860
with 1 mM methylglyoxal, GDH activity significantly decreases at 30 min of incubation, and markedly drops by 37% within 5 h compared to control
additional information
-
no inhibition or activation in the presence of ADP, GTP and leucine
-
additional information
-
complex inhibition pattern for ATP, GTP, NaCl, KCl, sodium acetate, NaI, and potassium nitrate of forward and reverse reaction at 5C and 37C
-
additional information
-
GDH2 is resistant to GTP inhibition
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
-
2fold activation
8-azidoguanosine 5'-diphosphate
-
used for affinity photolabeling
ADP
-
activation only if concentrations of both NAD(P)+ and substrate are high
ADP
-
above pH 7.0: allosteric activation; pH 6.0-7.0: strong inhibition
ADP
-
stimulation
ADP
-
stimulation
ADP
-
1.5fold activation, 0.08 mM NADH as cofactor
ADP
-
stimulation
ADP
-
stimulation
ADP
-
1 mM, approx. 2fold activation of membrane-bound liver enzyme
ADP
-
no activation of R463A mutant enzyme
ADP
-
1 mM, pH 8.0, 3fold activation of wild-type enzyme, no significant actication of Tyr187 mutant enzymes
ADP
-
activates in presence of 3 M NaCl or 3 M KCl or in absence of salts
ADP
-
increases the activity up to 2.3fold
ADP
-
0.1-1.0 mM, activates wild-type enzyme and mutant enzyme E279G
ADP
-
activates
ADP
P49448
in absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu
ADP
P10860
120.88% activity in the presence of 0.25 mM ATP
ADP
-
activation at 1 mM
ADP
-
activates at 1 mM
ADP
-
ADP activation is almost abolished after treatment with TLCK-treated chymotrypsin
ADP
P10860
ADP induces an allosteric conformational change in GDH1, leading to a 2fold enhanced oxidative deamination
ADP
-
ADP displays a lower affinity for hGDH2 than for hGDH1
ADP
P49448
positive allosteric regulator
ADP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
ADP
-
allosteric activator, addition of ADP or leucine to the single cofactor assay results in a marked activation of NADPH oxidation, about 1100% activation by ADP. Relative activation by ADP of GDH-catalyzed NAD+reduction is 36%, compared with 198% for NADP+ reduction
AMP
-
1 mM, reaction velocity increases 15fold at saturating NAD+ and glutamate levels
AMP
-
activates NADH-linked glutamate synthesis, inhibits NADPH-linked activity; activation only in biosynthetic direction
ATP
-
4.8fold activation, cofactor 0.08 mM NADH
ATP
-
approx. 1.5fold activation of membrane-bound liver enzyme
ATP
-
wild-type: activation at 1 mM, inhibition below and above, H454Y and S448P mutant enzymes: progressive increase in activity until 10 mM, inhibition above
ATP
-
activates in presence of 3 M NaCl or in absence of salts, slight inhibition in presence of 3 M KCl
ATP
-
allosteric regulation, weak stimulation of the deamination reaction and strong activation of the amination reaction
Chymotrypsin
-
0.2 mg/ml chymotrypsin cleaves glutamate dehydrogenase in such a fashion as to cause a rise in activity with NADP+ and NAD+ as coenzyme, over threefold activation in the NADP+ assay with TLCK-treated chymotrypsin, the distinguishing aspect with untreated chymotrypsin is that the activation is followed by a decrease in activity
-
glutathione
-
2fold activation
GTP
-
inhibition at pH 9.0, activation in presence of electrolytes at pH 6.0
KCl
-
activates at 5C and 37C
L-aspartate
-
2fold activation of glutamate synthesis
L-His
-
activates in presence of 3 M NaCl, 3 M Kcl or in absence of salts
L-Leu
-
activates in presence of 3 M NaCl, 3 M Kcl or in absence of salts
L-Leu
P49448
0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1; 0.3-10 mM stimulates isoenzyme GLUD2 to a greater extent than isoenzyme GLUD1. In absence of GTP the isoenzyme GLUD2 assumes a conformational state associated with little catalytic activity, it remains amenable to full activation by ADP and/or L-Leu
L-leucine
-
-
L-leucine
-
L-leucine displays the same affinity for hGDH2 and hGDH1
L-leucine
-
allosteric activator, addition of ADP or leucine to the single cofactor assay results in a marked activation of NADPH oxidation, about 725% activation by L-leucine, respectively. Activation of NAD+ and NADP+ reduction by 40% and 135%, respectively
leucine
-
activates at 5C only
leucine
-
wild-type, S448P, H454Y and R463A mutant enzymes
leucine
P10860
with 10 mM the activity increases by 1.55fold after 240 min and by 1.24fold when the enzyme is preincubated with methylglyoxal
leucine
P10860
enhances the oxidative deamination reaction of GDH1
leucine
-
the enzyme is subject to allosteric activation by leucine invlving ARg134, and Asp185, structural mechanism, overview
N6-(2-aminoethyl)-NAD+
-
-
N6-(2-aminoethyl)-NADP+
-
-
N6-(2-Hydroxy-3-trimethylammonium propyl)-NAD+
-
-
N6-(3-sulfonatopropyl)-NAD+
-
-
NaCl
-
activates at 37C only
phosphate
-
activator at pH 8.0-9.0, inhibitor at pH 6.0-7.6
PMP-BCATm
P10860
pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm) accelerates the oxidative deamination reaction of GDH1in the presence of branched-chain amino acids (Leu, Ile, Val). Reductive amination reaction is not affected
-
Poly(ethylene glycol)-N6-(2-aminoethyl)-NAD+
-
-
-
Poly(ethylene glycol)-N6-(2-aminoethyl)-NADP+
-
-
-
Trypsin
-
limited trypsin proteolyis activates the purified enzyme 8fold if the peptide is absent from the assay mixture, the native enzyme is 3fold activated if the cleaved peptide is present, activation may therefore be induced by loss of the peptide from the subunit of the native enzyme
-
leucine
-
the enzyme is subject to allosteric activation by leucine, structural mechanism, overview
additional information
-
serum GLDH activity is elevated in alcohol abuse
-
additional information
-
not inhibited by trypsin
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
2-oxoglutarate
-
euthermic animal, assay at 37C
0.14
2-oxoglutarate
-
NADP-linked reductive amination
0.18
2-oxoglutarate
-
reductive amination, low-activity form of the enzyme
0.2
2-oxoglutarate
-
reductive amination, high-activity form of the enzyme
0.2
2-oxoglutarate
-
cosubstrate NADPH
0.2
2-oxoglutarate
O59650
pH 7.6, 70C, recombinent enzyme (unheated)
0.25
2-oxoglutarate
-
NADPH-dependent activity
0.25
2-oxoglutarate
-
concentration range: 0.3-4.0 mM
0.25
2-oxoglutarate
O59650
pH 7.6, 70C, native enzyme
0.3
2-oxoglutarate
O59650
pH 7.6, 70C, recombinent enzyme (heated)
0.36
2-oxoglutarate
-
NADH + NH4Cl
0.36
2-oxoglutarate
-
isozyme 1, amination activity, cofactor NADH
0.4
2-oxoglutarate
-
50 mM Tris-HCl, pH 7.2
0.43
2-oxoglutarate
-
hibernating animal, assay at 5C
0.47
2-oxoglutarate
-
NADPH + NH4Cl
0.53
2-oxoglutarate
-
pH 7.6, 90C
0.59
2-oxoglutarate
-
isozyme 3, amination activity, cofactor NADH
0.6
2-oxoglutarate
-
cosubstrate NADH
0.62
2-oxoglutarate
-
glutamate dehydrogenase 2, 0.1 mM NADH
0.63
2-oxoglutarate
-
NADPH-dependent amination
0.64
2-oxoglutarate
-
NADPH-dependent amination
0.7
2-oxoglutarate
-
NADPH-dependent amination
0.7
2-oxoglutarate
-
cofactor NADH
0.98
2-oxoglutarate
-
hibernating animal, assay at 37C
1
2-oxoglutarate
-
liver enzyme
1.1
2-oxoglutarate
-
glutamate dehydrogenase 2, 80 mM NH4+
1.16
2-oxoglutarate
-
mutant C274G, hGDH1
1.2
2-oxoglutarate
-
500 mM Tris-HCl, pH 7.2
1.23
2-oxoglutarate
-
isozyme 2, amination activity, cofactor NADH
1.25
2-oxoglutarate
-
pH 8.0, 25C, wild-type enzyme
1.25
2-oxoglutarate
-
25C, wild-type enzyme
1.25
2-oxoglutarate
-
pH 8.0, 25C, wild-type enzyme hGDH1
1.25
2-oxoglutarate
-
wild-type, hGDH1
1.25
2-oxoglutarate
-
hGDH1, wild-type
1.25
2-oxoglutarate
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
1.25
2-oxoglutarate
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
1.27
2-oxoglutarate
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
1.29
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme Y187E
1.29
2-oxoglutarate
-
25C, mutant enzyme K333L
1.29
2-oxoglutarate
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
1.31
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme Y187M
1.31
2-oxoglutarate
-
25C, mutant enzyme K344L; 25C, mutant enzyme K346L
1.34
2-oxoglutarate
-
mutant C59G, hGDH1
1.34
2-oxoglutarate
-
hGDH1, mutant C323L
1.36
2-oxoglutarate
-
mutant C59Y, hGDH1
1.36
2-oxoglutarate
-
hGDH1, mutant C323Y
1.37
2-oxoglutarate
-
mutant C274Y, hGDH1
1.38
2-oxoglutarate
-
hGDH1, mutant C323M
1.39
2-oxoglutarate
-
pH 8.0, 25C, wild-type enzyme hGDH2
1.39
2-oxoglutarate
-
wild-type, hGDH2
1.39
2-oxoglutarate
-
hGDH1, mutant C323R; hGDH2, wild-type
1.39
2-oxoglutarate
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
1.39
2-oxoglutarate
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
1.4
2-oxoglutarate
-
-
1.4
2-oxoglutarate
-
assay at 37C
1.4
2-oxoglutarate
-
mutant C274A, hGDH1; mutant C59A, hGDH1
1.4
2-oxoglutarate
-
hGDH1, mutant C323G
1.4
2-oxoglutarate
-
pH 7.6, 60C
1.41
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme S443R hGDH2
1.41
2-oxoglutarate
-
hGDH2, mutant C323Y
1.44
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme Y187R
1.45
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme Y187G
1.45
2-oxoglutarate
-
25C, mutant enzyme K337L
1.45
2-oxoglutarate
-
hGDH2, mutant C323L; hGDH2, mutant C323M
1.46
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme Y187S
1.47
2-oxoglutarate
-
25C, mutant enzyme S445L
1.5 - 2
2-oxoglutarate
-
hGDH2, mutant C323G
1.5
2-oxoglutarate
-
25C, mutant enzyme G446D
1.5
2-oxoglutarate
-
hGDH2, mutant C323R
1.5
2-oxoglutarate
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
1.51
2-oxoglutarate
-
glutamate dehydrogenase 1, 0.1 mM NADH; glutamate dehydrogenase 1, 400 mM NH4+
1.54
2-oxoglutarate
-
isozyme 1, amination activity, cofactor NADPH
1.58
2-oxoglutarate
-
mutant C274G, hGDH2; mutant C59Y, hGDH2
1.59
2-oxoglutarate
-
mutant C274A, hGDH2
1.61
2-oxoglutarate
-
mutant C59A, hGDH2
1.66
2-oxoglutarate
-
mutant C274Y, hGDH2
1.67
2-oxoglutarate
-
mutant C59G, hGDH2
1.73
2-oxoglutarate
-
isozyme 3, amination activity, cofactor NADH
1.85
2-oxoglutarate
-
isozyme 2, amination activity, cofactor NADPH
1.86
2-oxoglutarate
-
mutant C119Y, hGDH1
1.9
2-oxoglutarate
-
mutant C119A, hGDH1
1.94
2-oxoglutarate
-
mutant C119G, hGDH1
2
2-oxoglutarate
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
2.1
2-oxoglutarate
-
cosubstrate NADPH
2.1
2-oxoglutarate
-
glutamate dehydrogenase 1, 40 mM NH4+
2.1
2-oxoglutarate
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
2.12
2-oxoglutarate
-
mutant C119A, hGDH2
2.18
2-oxoglutarate
-
mutant C119G, hGDH2
2.26
2-oxoglutarate
-
mutant C119Y, hGDH2
2.3
2-oxoglutarate
-
kidney enzyme
2.4
2-oxoglutarate
-
-
2.6
2-oxoglutarate
-
glutamate dehydrogenase 1, 0.2 mM NADPH
3.13
2-oxoglutarate
-
25C, mutant enzyme H454Y
3.3
2-oxoglutarate
-
cosubstrate NADH
3.5
2-oxoglutarate
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
3.66
2-oxoglutarate
-
euthermic animal, assay at 5C
3.7
2-oxoglutarate
-
glutamate dehydrogenase 1, 0.2 mM NADH; glutamate dehydrogenase 2, 0.2 mM NADPH
4
2-oxoglutarate
-
cofactor NADPH
4.5
2-oxoglutarate
-
cofactor NADH
5
2-oxoglutarate
-
NADH-dependent activity
6.3
2-oxoglutarate
-
cofactor NADPH
7.1
2-oxoglutarate
-
NAD-linked reductive amination
7.1
2-oxoglutarate
-
pH 8.0
10.5
2-oxoglutarate
-
-
10.5
2-oxoglutarate
-
assay at 5C
14
2-oxoglutarate
-
500 mM Tris-HCl, pH 8.2
0.00294
alpha-ketoglutarate
-
-
0.25
glutamate
-
hibernating animal, assay at 5C
0.32
glutamate
-
concentration range: 0.05-1.0 mM
0.47
glutamate
-
assay at 5C
0.5
glutamate
-
euthermic animal, assay at 5C
2.03
glutamate
-
euthermic animal, assay at 37C
2.1
glutamate
-
-
2.6
glutamate
-
assay at 37C
4.61
glutamate
-
mitochondrial enzyme, cofactor NAD+
5.2
glutamate
-
hibernating animal, assay at 37C
5.5
glutamate
-
concentration range: 1.0-10.0 mM
5.93
glutamate
-
enzyme from rough ER, cofactor NAD+
12
glutamate
-
cosubstrate NAD+
20.7
glutamate
-
mitochondrial enzyme, cofactor NADP+
23.8
glutamate
-
enzyme from rough ER, cofactor NADP+
0.24
L-glutamate
-
at pH 8.5
0.3
L-glutamate
-
cosubstrate NAD+
0.3
L-glutamate
-
pH 8.0, 70C
0.4
L-glutamate
-
kidney enzyme
0.6
L-glutamate
-
pH 7.6, 90C
0.64
L-glutamate
-
isozyme 1, deamination activity
0.74
L-glutamate
-
-
1
L-glutamate
-
1 mM, NAD+
1.01
L-glutamate
-
at pH 7.4
1.1
L-glutamate
-
cosubstrate NADP+
1.6
L-glutamate
-
cofactor NADP+
1.66
L-glutamate
-
cofactor NAD+
1.7
L-glutamate
-
50 mM Tris-HCl, pH 7.2
1.77
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2D172Y
1.81
L-glutamate
-
pH 9.5, 25C, wild-type enzyme hGDH2
2.4
L-glutamate
-
NADP-linked oxidative deamination
2.5
L-glutamate
-
pH 7.6, 60C
2.98
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K130Y
3
L-glutamate
-
1 mM, NADP+
3
L-glutamate
-
isozyme 3, deamination activity
3
L-glutamate
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
3.44
L-glutamate
-
pH 9.5, 25C, wild-type enzyme hGDH1
3.44
L-glutamate
-
pH 9.5, 25C, wild-type enzyme
3.52
L-glutamate
-
isozyme 2, deamination activity
3.65
L-glutamate
-
oxidative deamination, low-activity form of the enzyme
3.71
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1D172Y
3.76
L-glutamate
-
pH 9.5, 25C, mutant enzyme E279M
3.83
L-glutamate
-
oxidative deamination, high-activity form of the enzyme
3.94
L-glutamate
-
pH 9.5, 25C, mutant enzyme E279Y
3.98
L-glutamate
-
pH 9.5, 25C, mutant enzyme E279G
4.05
L-glutamate
-
pH 9.5, 25C, mutant enzyme E279L
4.12
L-glutamate
-
pH 9.5, 25C, mutant enzyme E279R
5.51
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K130Y
7.3
L-glutamate
-
NAD-linked oxidative deamination
7.99
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K94Y
10
L-glutamate
-
NADP+-dependent activity
10.41
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K118Y
10.7
L-glutamate
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
10.8
L-glutamate
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
12.4
L-glutamate
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
17.75
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2G96Y
19.5
L-glutamate
-
500 mM Tris-HCl, pH 9.4
21.82
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K94Y
25
L-glutamate
-
0.004 mM, NAD+
25.82
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K118Y
30.55
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1G96Y
0.291
N6-(2-aminoethyl)-NAD+
-
-
0.273
N6-(2-aminoethyl)-NADP+
-
-
0.148
N6-(2-hydroxy-2-trimethylammoniumpropyl)-NAD+
-
-
0.052
N6-(3-sulfonatopropyl)-NAD+
-
-
0.014
NAD+
-
-
0.016
NAD+
-
50 mM Tris-HCl, pH 7.2
0.02
NAD+
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
0.032
NAD+
-
kidney enzyme
0.063
NAD+
-
+ L-glutamate
0.1
NAD+
-
pH 8.0, 25C, recombinant enzyme
0.11
NAD+
-
500 mM Tris-HCl, pH 9.4
0.11
NAD+
-
pH 8.0, 25C, native enzyme
0.15
NAD+
-
500 mM Tris-HCl, pH 7.2
0.175
NAD+
-
-
0.2
NAD+
-
isozyme 1, deamination activity
0.26
NAD+
-
isozyme 2, deamination activity
0.32
NAD+
-
isozyme 3, deamination activity
0.364
NAD+
-
mitochondrial enzyme
0.4
NAD+
-
pH 8.0, 70C
0.43
NAD+
-
oxidative deamination, low-activity form of the enzyme
0.46
NAD+
-
-
0.53
NAD+
-
substrate L-glutamate
0.55
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K94Y
0.58
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2G96Y
0.59
NAD+
-
pH 9.5, 25C, wild-type enzyme hGDH2
0.63
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2D172Y
0.65
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1G96Y
0.71
NAD+
-
pH 9.5, 25C, wild-type enzyme hGDH1
0.71
NAD+
-
pH 9.5, 25C, wild-type enzyme
0.75
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K130Y
0.76
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1D172Y
0.79
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K94Y
0.82
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K118Y
0.92
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K130Y
0.924
NAD+
-
enzyme from rough ER
0.94
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K118Y
2.44
NAD+
-
oxidative deamination, high-activity form of the enzyme
3
NAD+
-
NAD-linked oxidative deamination
6.94
NAD+
-
pH 9.5, 25C, mutant enzyme E279G
7.6
NAD+
-
pH 9.5, 25C, mutant enzyme E279R
8.35
NAD+
-
pH 9.5, 25C, mutant enzyme E279Y
9.98
NAD+
-
pH 9.5, 25C, mutant enzyme E279M
10.01
NAD+
-
pH 9.5, 25C, mutant enzyme E279L
0.000175
NADH
-
-
0.004
NADH
-
50 mM Tris-HCl, pH 7.2
0.007
NADH
-
+ 2-oxoglutarate
0.0083
NADH
-
-
0.009
NADH
-
glutamate dehydrogenase 1, 5 mM 2-oxoglutarate; glutamate dehydrogenase 2, 5 mM 2-oxoglutarate
0.01
NADH
-
500 mM Tris-HCl, pH 8.2
0.012
NADH
-
glutamate dehydrogenase 2, 80 mM NH4+
0.012
NADH
-
500 mM Tris-HCl, pH 7.2
0.015
NADH
-
liver enzyme
0.02
NADH
-
glutamate dehydrogenase 1, 40 mM NH4+
0.02
NADH
-
-
0.022
NADH
-
kidney enzyme
0.04
NADH
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
0.048
NADH
-
glutamate dehydrogenase 1, 400 mM NH4+
0.05
NADH
-
glutamate dehydrogenase 1, 12.5 mM 2-oxoglutarate
0.064
NADH
-
pH 8.0
0.07
NADH
-
isozyme 1, amination activity, cofactor NADH
0.075
NADH
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
0.076
NADH
-
25C, mutant enzyme K346L
0.079
NADH
-
25C, mutant enzyme K333L
0.08
NADH
-
pH 8.0, 25C, wild-type enzyme
0.08
NADH
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
0.081
NADH
-
25C, wild-type enzyme
0.081
NADH
-
pH 8.0, 25C, wild-type enzyme hGDH1
0.081
NADH
-
wild-type, hGDH1
0.081
NADH
-
hGDH1, wild-type
0.081
NADH
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
0.081
NADH
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
0.082
NADH
-
pH 8.0, 25C, mutant enzyme Y187E; pH 8.0, 25C, mutant enzyme Y187R
0.083
NADH
-
pH 7.6, 90C
0.084
NADH
-
pH 8.0, 25C, mutant enzyme Y187M
0.085
NADH
-
pH 8.0, 25C, mutant enzyme Y187G
0.086
NADH
-
pH 8.0, 25C, wild-type enzyme hGDH2
0.086
NADH
-
wild-type, hGDH2
0.086
NADH
-
hGDH2, wild-type
0.086
NADH
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
0.086
NADH
-
isozyme GDH2, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
0.088
NADH
-
pH 8.0, 25C, mutant enzyme Y187S
0.088
NADH
-
25C, mutant enzyme K337L
0.088
NADH
-
pH 8.0, 25C, mutant enzyme S443R hGDH2
0.089
NADH
-
25C, mutant enzyme G446D
0.09
NADH
-
isozyme 3, amination activity, cofactor NADH
0.09
NADH
-
concentration range: 0.04-0.1 mM
0.09
NADH
-
25C, mutant enzyme K344L
0.09
NADH
-
mutant C119A, hGDH1
0.091
NADH
-
mutant C119Y, hGDH1
0.092
NADH
-
mutant C119G, hGDH1
0.094
NADH
-
mutant C59G, hGDH1
0.097
NADH
-
mutant C59A, hGDH1
0.098
NADH
-
25C, mutant enzyme S445L
0.098
NADH
-
mutant C119G, hGDH2
0.099
NADH
-
mutant C59A, hGDH2; mutant C59Y, hGDH1
0.101
NADH
-
mutant C119A, hGDH2
0.102
NADH
-
mutant C59Y, hGDH2
0.106
NADH
-
mutant C59G, hGDH2
0.108
NADH
-
mutant C119Y, hGDH2
0.11
NADH
-
-
0.117
NADH
-
hGDH1, mutant C323L
0.119
NADH
-
hGDH1, mutant C323G; hGDH1, mutant C323M; hGDH2, mutant C323M
0.121
NADH
-
hGDH2, mutant C323L
0.122
NADH
-
25C, mutant enzyme H454Y
0.122
NADH
-
hGDH1, mutant C323R
0.125
NADH
-
hGDH2, mutant C323R
0.128
NADH
-
hGDH2, mutant C323G
0.129
NADH
-
hGDH1, mutant C323Y
0.13
NADH
-
reductive amination, low-activity form of the enzyme
0.138
NADH
-
hGDH2, mutant C323Y
0.14
NADH
-
isozyme 2, amination activity, cofactor NADH
0.14
NADH
-
pH 7.6, 50C
0.169
NADH
-
mutant C274A, hGDH2
0.175
NADH
-
mutant C274G, hGDH2
0.176
NADH
-
mutant C274Y, hGDH2
0.178
NADH
-
mutant C274Y, hGDH1
0.181
NADH
-
mutant C274G, hGDH1
0.189
NADH
-
mutant C274A, hGDH1
0.2
NADH
-
NAD-linked reductive amination
0.5
NADH
-
NADH-dependent activity
0.52
NADH
-
reductive amination, high-activity form of the enzyme
0.98
NADH
-
substrate 2-oxoglutarate
0.004
NADP+
-
NADP+-dependent activity
0.013
NADP+
-
oxidative deamination, low-activity form of the enzyme
0.019
NADP+
-
NADP-linked oxidative deamination
0.025
NADP+
-
+ L-glutamate
0.025
NADP+
-
pH 7.6, 90C
0.028
NADP+
-
cosubstrate glutamate
0.029
NADP+
-
oxidative deamination, high-activity form of the enzyme
0.035
NADP+
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
0.08
NADP+
-
concentration range: 0.02-0.2 mM
0.1
NADP+
-
pH 8.0, 70C
0.16
NADP+
-
-
0.18
NADP+
-
substrate L-glutamate
0.31
NADP+
-
cosubstrate norvaline
0.443
NADP+
-
enzyme from rough ER
0.637
NADP+
-
mitochondrial enzyme
0.006
NADPH
-
NADPH-dependent amination
0.01
NADPH
-
+ 2-oxoglutarate
0.01
NADPH
-
pH 7.6, 60C
0.011
NADPH
-
reductive amination, low-activity form of the enzyme
0.011
NADPH
-
-
0.013
NADPH
-
NADPH-dependent activity
0.013
NADPH
-
NADP-linked reductive amination
0.013
NADPH
-
reductive amination, high-activity form of the enzyme
0.018
NADPH
-
NADPH-dependent amination
0.02
NADPH
-
-
0.02
NADPH
-
NADPH-dependent amination
0.022
NADPH
-
-
0.028
NADPH
-
glutamate dehydrogenase 1, 10 mM 2-oxoglutarate; glutamate dehydrogenase 2, 10 mM 2-oxoglutarate
0.037
NADPH
-
pH 7.6, 90C
0.04
NADPH
-
concentration range: 0.002-0.1 mM
0.04
NADPH
O59650
pH 7.6, 70C, native enzyme
0.05
NADPH
O59650
pH 7.6, 70C, recombinent enzyme (heated)
0.069
NADPH
-
glutamate dehydrogenase 1, 40 mM NH4+; glutamate dehydrogenase 2, 80 mM NH4+
0.1
NADPH
O59650
pH 7.6, 70C, recombinent enzyme (unheated)
0.13
NADPH
-
-
0.17
NADPH
-
50 mM Tris-HCl, pH 7.2
0.27
NADPH
-
isozyme 1, amination activity, cofactor NADPH
0.42
NADPH
-
pH 8.0
0.46
NADPH
-
isozyme 3, amination activity, cofactor NADPH
0.54
NADPH
-
500 mM Tris-HCl, pH 7.2
0.56
NADPH
-
substrate 2-oxoglutarate; substrate NH3
0.75
NADPH
-
500 mM Tris-HCl, pH 8.2
0.78
NADPH
-
isozyme 2, amination activity, cofactor NADPH
2.5
NH3
O59650
pH 7.6, 70C, recombinent enzyme (unheated)
9.5
NH3
-
cofactor NADPH
10
NH3
-
in situ activity in 50 mM Tris-HCl buffer and 2 mM EDTA, pH 8, at 37C
11.4
NH3
O59650
pH 7.6, 70C, recombinent enzyme (heated)
12.8
NH3
-
hGDH1, pH 8.0, temperature not specified in the publication
13
NH3
O59650
pH 7.6, 70C, native enzyme
13.4
NH3
-
wild type isozyme GDH1, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
14.7
NH3
-
hGDH2, pH 8.0, temperature not specified in the publication
17.1
NH3
-
wild type isozyme GDH2, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
22.2
NH3
-
mutant enzyme R443S/G456A, in 50 mM triethanolamine buffer (pH 8.0), 2.6 mM EDTA, 1.4 mM NADP+, and 1 mM ADP
33
NH3
-
hGDH2, pH 7.5, temperature not specified in the publication
35
NH3
-
hGDH1, pH 7.5, temperature not specified in the publication
57.5
NH3
-
hGDH1, pH 7.0, temperature not specified in the publication
62.2
NH3
-
hGDH2, pH 7.0, temperature not specified in the publication
68
NH3
-
pH 8.0
0.0424
NH4+
-
-
1.3
NH4+
-
concentration range: 0.2-5 mM
2.82
NH4+
-
pH 7.6, 90C
3.2
NH4+
-
-
4.1
NH4+
-
-
4.1
NH4+
-
assay at 5C
5.8
NH4+
-
glutamate dehydrogenase 1, 0.2 mM NADPH
6.5
NH4+
-
-
7
NH4+
-
glutamate dehydrogenase 1, 0.2 mM NADPH
7
NH4+
-
euthermic animal, assay at 37C
10.4
NH4+
-
glutamate dehydrogenase 1, 10 mM 2-oxoglutarate
12.1
NH4+
-
hibernating animal, assay at 5C
12.9
NH4+
-
glutamate dehydrogenase 2, 5 mM 2-oxoglutarate
13
NH4+
-
isozyme 2, amination activity, cofactor NADH
13
NH4+
-
concentration range: 10-200 mM
15
NH4+
-
cosubstrates NADPH + 2-oxoglutarate
15.8
NH4+
-
glutamate dehydrogenase 1, 5 mM 2-oxoglutarate
15.8
NH4+
-
hibernating animal, assay at 37C
17.8
NH4+
-
-
17.8
NH4+
-
assay at 37C
19
NH4+
-
glutamate dehydrogenase 1, 10 mM 2-oxoglutarate
21.7
NH4+
-
glutamate dehydrogenase 1, 0.1 mM NADH
22.8
NH4+
-
glutamate dehydrogenase 1, 0.1 mM NADH
24.7
NH4+
-
euthermic animal, assay at 5C
27
NH4+
-
cosubstrates NADH + 2-oxoglutarate
30
NH4+
-
isozyme 1, amination activity, cofactor NADH
36
NH4+
-
isozyme 1, amination activity, cofactor NADPH
41
NH4+
-
isozyme 3, amination activity, cofactor NADPH
44
NH4+
-
isozyme 3, amination activity, cofactor NADH
53
NH4+
-
isozyme 2, amination activity, cofactor NADPH
58
NH4+
-
500 mM Tris-HCl, pH 8.2
77
NH4+
-
500 mM Tris-HCl, pH 7.2
106
NH4+
-
glutamate dehydrogenase 1, 12.5 mM 2-oxoglutarate
115.1
NH4+
-
glutamate dehydrogenase 1, 0.2 mM NADH
160
NH4+
-
50 mM Tris-HCl, pH 7.2
0.38
NH4Cl
-
biphasic Lineweaver-Burk plot suggests 2 Km values
1.25
NH4Cl
-
reductive amination, high-activity form of the enzyme
1.31
NH4Cl
-
reductive amination, low-activity form of the enzyme
1.5
NH4Cl
-
NADPH-dependent amination
1.7
NH4Cl
-
NADP-linked reductive amination
2.4
NH4Cl
-
NADPH-dependent amination
2.9
NH4Cl
-
NADPH-dependent amination
4.9
NH4Cl
-
NAD-linked reductive amination
5.1
NH4Cl
-
NADP-linked reductive amination
20
NH4Cl
-
kidney enzyme
21
NH4Cl
-
liver enzyme
28
NH4Cl
-
cofactor NADH
41
NH4Cl
-
cofactor NADPH
44
NH4Cl
-
NADPH + 2-oxoglutarate
50
NH4Cl
-
NADH + 2-oxoglutarate
66
NH4Cl
-
NADH-dependent activity
100
NH4Cl
-
biphasic Lineweaver-Burk plot suggests 2 Km values
49
norvaline
-
-
0.444
poly(ethyleneglycol)-N6-(2-aminoethyl)-NAD+
-
-
-
0.425
poly(ethyleneglycol)-N6-(2-aminoethyl)-NADP+
-
-
-
31
L-glutamate
-
500 mM Tris-HCl, pH 7.2
additional information
additional information
-
Km-values for 2-oxoglutaratefor mutant enzyme R443S, recombinant wild-type enzyme and wild-type enzyme from human liver
-
additional information
additional information
-
-
-
additional information
additional information
P26443
kinetic analysis in wild-type and transgenic overexpressing brain cell fractions, overview
-
additional information
additional information
-
lowering the pH of the buffer from pH 8.0 to pH 7.0 increases the Km for ammonia substantially, i.e. for hGDH1 from 12.8 mM to 57.5 mM, and for hGDH2: from 14.7 mM to 62.2 mM, thus essentially precluding reductive amination
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
14
2-oxoglutarate
-
hGDH1, mutant C323Y
15
2-oxoglutarate
-
hGDH1, mutant C323R
17
2-oxoglutarate
-
hGDH1, mutant C323G; hGDH1, mutant C323L; hGDH2, mutant C323Y
19
2-oxoglutarate
-
hGDH1, mutant C323M; hGDH2, mutant C323M; hGDH2, mutant C323R
20
2-oxoglutarate
-
hGDH2, mutant C323L
21
2-oxoglutarate
-
hGDH2, mutant C323G
50
2-oxoglutarate
-
-
104
2-oxoglutarate
-
pH 8.0, 25C, wild-type enzyme hGDH1
104
2-oxoglutarate
-
hGDH1, wild-type
130
2-oxoglutarate
-
pH 8.0, 25C, wild-type enzyme hGDH2
130
2-oxoglutarate
-
hGDH2, wild-type
134
2-oxoglutarate
-
pH 8.0, 25C, mutant enzyme S443R hGDH2
165.3
2-oxoglutarate
-
pH 7.6, 90C
183
2-oxoglutarate
-
cofactor NADH
195
2-oxoglutarate
-
concentration range: 0.3-4.0 mM
510
2-oxoglutarate
-
reduction
25
glutamate
-
oxidation
40
glutamate
-
concentration range: 0.05-1.0 mM
61
glutamate
-
cofactor NADP+
162
glutamate
-
concentration range: 1.0-10.0 mM
714
glutamate
-
cofactor NADH, + 1 mM ADP
2
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K130Y
3.33
L-glutamate
-
cofactor NAD+, value below 200.0
4
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K130Y
4.83
L-glutamate
-
cofactor NAD+
11
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K94Y
14
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K94Y
42
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1G96Y
48
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1K118Y
57
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH1D172Y; pH 9.5, 25C, mutant enzyme hGDH2D172Y; pH 9.5, 25C, mutant enzyme hGDH2G96Y
59
L-glutamate
-
pH 9.5, 25C, mutant enzyme hGDH2K118Y
65
L-glutamate
-
pH 9.5, 25C, wild-type enzyme hGDH1
83
L-glutamate
-
pH 9.5, 25C, wild-type enzyme hGDH2
121.2
L-glutamate
-
pH 7.6, 90C
2
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K130Y
4
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K130Y
11
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K94Y
14
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K94Y
42
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1G96Y
48
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1K118Y
51
NAD+
-
pH 9.5, 25C, mutant enzyme E279M
57
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH1D172Y; pH 9.5, 25C, mutant enzyme hGDH2D172Y; pH 9.5, 25C, mutant enzyme hGDH2G96Y
57
NAD+
-
pH 9.5, 25C, mutant enzyme E279L
59
NAD+
-
pH 9.5, 25C, mutant enzyme hGDH2K118Y
59
NAD+
-
pH 9.5, 25C, mutant enzyme E279G
61
NAD+
-
pH 9.5, 25C, mutant enzyme E279R
65
NAD+
-
pH 9.5, 25C, wild-type enzyme hGDH1
65
NAD+
-
pH 9.5, 25C, wild-type enzyme
68
NAD+
-
pH 9.5, 25C, mutant enzyme E279Y
83
NAD+
-
pH 9.5, 25C, wild-type enzyme hGDH2
77
NADH
-
mutant C119G, hGDH1
79
NADH
-
mutant C119Y, hGDH1
81
NADH
-
mutant C119A, hGDH1
85
NADH
-
mutant C59Y, hGDH1
88
NADH
-
mutant C274Y, hGDH1
90
NADH
-
concentration range: 0.04-0.1 mM
90
NADH
-
mutant C274A, hGDH1; mutant C59A, hGDH1
91
NADH
-
mutant C274G, hGDH1; mutant C59G, hGDH1
93
NADH
-
25C, mutant enzyme K333L
95
NADH
-
25C, mutant enzyme H454Y
98
NADH
-
25C, mutant enzyme K337L
100
NADH
-
25C, mutant enzyme K346L
100
NADH
-
mutant C274Y, hGDH2
101
NADH
-
mutant C119G, hGDH2
101
NADH
-
mutant enzyme M415L/R443S/G456A, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
102
NADH
-
25C, mutant enzyme G446D
103
NADH
-
mutant C119Y, hGDH2
104
NADH
-
25C, wild-type enzyme
104
NADH
-
pH 8.0, 25C, wild-type enzyme hGDH1
104
NADH
-
wild-type, hGDH1
104
NADH
-
wild type isozyme GDH1, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
104
NADH
-
isozyme GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
105
NADH
-
25C, mutant enzyme K344L
105
NADH
-
mutant C119A, hGDH2
108
NADH
-
mutant C59Y, hGDH2
109
NADH
-
mutant C274G, hGDH2
110
NADH
-
mutant C59G, hGDH2
111
NADH
-
25C, mutant enzyme S445L
114
NADH
-
mutant C274A, hGDH2
117
NADH
-
mutant C59A, hGDH2
118
NADH
-
mutant enzyme L415M/S443R/A456G, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
130
NADH
-
pH 8.0, 25C, wild-type enzyme hGDH2
130
NADH
-
wild-type, hGDH2
130
NADH
-
wild type isozyme GDH2, 50 mM triethanolamine pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0 at 25C
130
NADH
-
isozyme GDH2, in the presence of 1 mM ADP, in 50 mM triethanolamine, pH 8.0, 100 mM ammonium acetate, 0.1 mM NADH, and 2 mM EDTA, pH 8.0, at 25C
134
NADH
-
pH 8.0, 25C, mutant enzyme S443R hGDH2
374.5
NADH
-
pH 7.6, 90C
102
NADP+
-
concentration range: 0.02-0.2 mM
399.6
NADP+
-
pH 7.6, 90C
112
NADPH
-
concentration range: 0.002-0.1 mM
200
NADPH
-
NADPH-dependent activity
387.5
NADPH
-
pH 7.6, 90C
43.8
NH4+
-
pH 7.6, 90C
63.3
NH4+
-
concentration range: 0.2-5 mM
168
NH4+
-
concentration range: 10-200 mM
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
31
2-oxobutyrate
-
-
0.315
2-oxoglutarate
-
-
2.6
2-oxoglutarate
-
liver enzyme
5
2-oxoglutarate
-
kidney enzyme
60
2-oxoglutarate
-
substrate inhibition vs. NADPH
70
2-oxoglutarate
-
substrate inhibition vs. NH4+
24.4
2-oxovalerate
-
-
0.005
8-Azidoguanosine 5'-triphosphate
-
-
4
ADP
-
-
6.2
alanine
-
at pH 10.0
23.2
alanine
-
at pH 8.5
0.76
ATP
-
inhibition of microtubules to membrane-bound liver enzyme
0.00036
diethylstilbestrol
-
inhibition of recombinant H454Y mutant enzyme
0.00074
diethylstilbestrol
-
inhibition of recombinant S448P mutant enzyme
0.0017
diethylstilbestrol
-
inhibition of recombinant wild-type enzyme
0.0051
diethylstilbestrol
-
inhibition of recombinant R463A mutant enzyme
1.1
glutamate
-
at pH 10.0
4.1
glutamate
-
at pH 8.5
0.07
Glutarate
-
at pH 8.5
0.09
Glutarate
-
at pH 7.4
0.000042
GTP
-
inhibition of recombinant wild-type enzyme
0.00005
GTP
P10860
GTP alone
0.00022
GTP
-
inhibition of recombinant R463A mutant enzyme
0.0006
GTP
-
-
0.00156
GTP
P10860
molar ratio pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm)/GDH1: 1
0.0031
GTP
-
inhibition of recombinant S448P mutant enzyme
0.00312
GTP
P10860
molar ratio pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm)/GDH1: 2
0.0065
GTP
-
1 mM NAD+ or 80 mM NADH
0.00795
GTP
P10860
molar ratio pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm)/GDH1: 6
0.00806
GTP
P10860
molar ratio pyridoxamine 5'-phosphate-form of the mitochondrial branched chain aminotransferase (PMP-BCATm)/GDH1: 4
0.009
GTP
-
0.08 mM NADH
0.012
GTP
-
0.016 mM NADH
0.018
GTP
-
1 mM NADP+
0.21
GTP
-
inhibition of recombinant H454Y mutant enzyme
6.1
histidine
-
at pH 10.0
0.28
Isophthalate
-
-
6.3
L-glutamate
-
-
80
L-glutamate
-
reductive amination with NADPH, not with NADH is inhibited
3.7
lysine
-
at pH 10.0
9.3
lysine
-
at pH 8.5
0.3
NAD+
-
kidney enzyme
0.011
NADH
-
liver enzyme
0.016
NADH
-
kidney enzyme
0.24
NADP+
-
-
0.028
NADPH
-
-
2.9
NH4+
-
-
46
NH4Cl
-
liver enzyme
69
NH4Cl
-
kidney enzyme
78
norvaline
-
-
0.03
o-phthalaldehyde
-
vs. 2-oxoglutarate
0.1
o-phthalaldehyde
-
vs. NADH
0.36
oxalylglycine
-
vs. 2-oxoglutarate
0.54
oxalylglycine
-
vs. NADPH
0.9
oxalylglycine
-
vs. NH4+
0.000013
palmitoyl-CoA
-
inhibition of recombinant S448P mutant enzyme
0.000015
palmitoyl-CoA
-
inhibition of recombinant H454Y mutant enzyme
0.00003
palmitoyl-CoA
-
inhibition of recombinant wild-type enzyme
0.0002
palmitoyl-CoA
-
inhibition of recombinant R463A mutant enzyme
5
Phenylglyoxal
-
vs. 2-oxoglutarate
6
Phenylglyoxal
-
vs. NADH
0.0009 - 0.061
phosphatidylserine
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
Chloroquine
-
GDH1
0.14
Chloroquine
-
GDH2
0.00017
GTP
-
inhibition of wild-type enzyme and mutant enzymes r470H and N498S. No inhibition of mutant enzyme G456A. IC50 of mutant enzyme R470G is 0.00017 mM, IC50 of mutant enzyme N49
0.00019
GTP
-
inhibition of wild-type enzyme and mutant enzymes r470H and N498S. No inhibition of mutant enzyme G456A. IC50 of wild-type enzyme is 0.00019 mM
0.00019
GTP
P49448
potent inhibitor. IC50 for wild-type enzyme is 0.00019 mM
0.00031
GTP
-
in the absence of other modulators, pH 8.0
0.001
GTP
-
isozyme GDH1
0.00161
GTP
-
in the presence of 0.1 mM ADP, pH 8.0
0.0028
GTP
-
IC50 of mutant enzyme G456A is 0.0028 mM
0.0028
GTP
P49448
IC50 for mutant enzyme G456A is 0.0028 mM. ADP renders the GLUD1-derived enzyme less sensitive to GTP inhibition
0.0108
GTP
-
IC50 for mutant enzyme S331T: 0.0108 mM
0.0113
GTP
-
IC50 for mutant enzyme M370L: 0.0113 mM
0.0122
GTP
-
IC50 for wild-type GLUD1: 0.0122 mM
0.0147
GTP
-
IC50 for mutant enzyme M415L: 0.0147 mM
0.0162
GTP
-
IC50 for mutant enzyme R443S: 0.0162 mM
0.0185
GTP
-
in the presence of 1 mM ADP, pH 8.0
0.0239
GTP
-
in the presence of 0.1 mM ADP, pH 8.0
0.07
GTP
-
isozyme GDH2
0.0785
GTP
-
in the absence of other modulators, pH 8.0
0.1668
GTP
-
in the presence of 1 mM ADP, pH 8.0
0.186
GTP
-
mutant S448P, pH 8.0, 25C
0.227
GTP
-
mutant Q441R, pH 8.0, 25C
0.2627
GTP
-
wild-type, pH 8.0, 25C
0.31
GTP
-
GDH1, in the absence of ADP, in 50 mM triethanolamine pH 8.0 buffer
0.317
GTP
-
mutant S445L, pH 8.0, 25C
2.921
GTP
-
mutant H454Y, pH 8.0, 25C
18.5
GTP
-
GDH1, in the presence of 1 mM ADP, in 50 mM triethanolamine pH 8.0 buffer
78.5
GTP
-
GDH2, in the absence of ADP, in 50 mM triethanolamine pH 8.0 buffer in 50 mM TRA pH 8.0 buffer
139.4
GTP
-
mutant enzyme R443S/G456A, in the absence of ADP, in 50 mM triethanolamine pH 8.0 buffer
166.8
GTP
-
GDH2, in the presence of 1 mM ADP, in 50 mM triethanolamine pH 8.0 buffer
180
GTP
-
mutant K450E, pH 8.0, 25C
622.4
GTP
-
mutant enzyme R443S/G456A, in the absence of ADP, in 50 mM triethanolamine pH 8.0 buffer
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00076
-
activity in liver nuclei, cofactor NADH
0.0028
-
activity in liver mitochondria, cofactor NADH
0.168
-
NADH dependent activity in cells grown on medium containing 1 mM NH4Cl
0.257
-
NADH dependent activity in cells grown on medium containing 1 mM NH4Cl
0.336
-
NADH dependent activity in cells grown on medium containing 1 mM NH4Cl
0.36
-
cofactor NADPH
0.858
-
NADPH dependent activity in cells grown on medium containing 1 mM NH4Cl
1.07
-
NADH dependent activity in cells grown on medium containing 1 mM NH4Cl
1.2
-
glutamate dehydrogenase 2
1.8
-
glutamate dehydrogenase 1
1.93
-
after 3rd crystallization
1.96
-
NADPH dependent activity in cells grown on medium containing 1 mM NH4Cl
2.22
-
NADPH dependent activity in cells grown on medium containing 1 mM NH4Cl
3.5
-
cofactor NADH
4
-
cofactor NADPH
4.6
-
membrane-bound liver enzyme
4.8
-
enzyme purified from liver nuclei
5.18
-
NADPH dependent activity in cells grown on medium containing 1 mM NH4Cl
5.9
-
low-activity form of the enzyme, NADP+ dependent deamination
13
-
cofactor NADH
17.8
-
liver enzyme
19
-
recombinant S448P mutant enzyme, basal activity
32.3
-
high-activity form of the enzyme, NADP+-dependent deamination
32.5
-
at 85C
34
-
liver enzyme
55
-
recombinant S448P mutant enzyme, maximal activity in the presence of 6 mM leucine
69
-
recombinant S448P mutant enzyme, maximal activity in the presence of 0.2 mM ADP
73
-
recombinant R463A mutant enzyme, basal activity
74
-
recombinant H454Y mutant enzyme, basal activity
79.4
-
purified enzyme, pH 8.0, 70C
84
-
recombinant wild-type enzyme, basal activity
100
-
recombinant R463A mutant enzyme, maximal activity in the presence of 6 mM leucine
126.4
-
cofactor NADH
130
-
recombinant S448P mutant enzyme, maximal activity in the presence of 6 mM leucine; recombinant wild-type enzyme, maximal activity in the presence of 0.2 mM ADP or 6 mM leucine
140
-
recombinant H454Y mutant enzyme, maximal activity in the presence of 0.2 mM ADP
145.7
-
purified mutant enzyme R443S/G456A
159.1
-
purified isozyme GDH2
161.9
-
purified isozyme GDH1
190
-
enzyme from euthermic animals
201
-
enzyme from hibernating animals
411
-
native enzyme at 100C
419
-
recombinant enzyme at 75C
423
-
recombinant enzyme at 90C
additional information
-
0.263 DELTA absorbance/min/mg, cofactor NADP+; 1.44 DELTA absorbance/min/mg, cofactor NAD+
additional information
-
-
additional information
-
hGDH1 displays a high basal activity of 40% of its maximal activity. Regulation of the hGDH1 activity is achieved by interplay of GTP and ADP/L-leucine; hGDH2 displays a basal activity less than 10% of its maximal activity. Control of the hGDH2 activity depends on the level of its basal activity and on changing ADP/L-leucine concentrations. For hGDH2 enzyme protein concentration and basal activity show a linear pattern of dependence. Lowering the temperature of the reaction mixture from 25C to 20C has a stabilizing effect on hGDH2, as under these conditions, the specific basal activities of the enzyme increases. Increasing the concentration of the TrisHCl buffer from 50 mM to 125 mM or to 250 mM (pH 8.0) raises basal activity levels, but the maximal activity declines
additional information
P26443
enzyme activity in wild-type and transgenic overexpressing brain cell fractions, overview
additional information
O59650
the specific activity of the hexameric form of the recombinant enzyme is much lower than that of the natural enzyme. The structure of the hexameric form of the recombinant enzyme with low specific activity (Type I) is different from that of the natural enzyme with high specific activity (Type II). Upon heat treatment (80C, 15 min), the Type I structure is effectively converted to Type II structure and the specific activity of the enzyme is increased by 2.6fold
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.4
-
NADPH + NH3 + 2-oxoglutarate
6.75
-
NADPH + NH3 + 2-oxoglutarate
7
P10860
reductive amination at
7.4
-
NADH + 2-oxoglutarate + NH3
7.4
P26443
assay at
7.5 - 8
-
isozyme GDH1
7.5
-
NADP+ + L-glutamate, NADH + NH3 + 2-oxoglutarate
7.5
-
isozyme GDH2
7.5
-
in TRA buffer hGDH2 displays its maximal activity and its highest basal activity at pH 7.5
7.6
-
in the absence of phosphate
7.6
-
NADPH
7.6
-
NADP+ + glutamate
7.6
-
NAD(P)H + 2-oxoglutarate + NH3
7.6
O59650
assay at
7.7
-
NADPH + 2-oxoglutarate + NH3
7.7
-
NADPH + 2-oxoglutarate + NH3
7.7
-
with NAD(P)H
7.8 - 8.4
-
-
7.8
-
2-oxoglutarate + NH3 + NAD(P)H, liver enzyme
7.8
-
NADH + NH3 + 2-oxoglutarate
7.8
-
highest basal activity in phosphate buffer
7.95
-
NADPH-dependent amination
8
-
NADPH + 2-oxoglutarate + NH3
8
-
NAD+ + L-glutamate
8
-
reductive amination
8
-
amination reaction
8
P10860
oxidative deamination at
8
-
assay at
8
-
glutamate oxidation
8
-
higher activity than at pH 7.0
8
-
assay at
8.05
-
NADPH-dependent amination
8.2
-
NADH + NH3 + 2-oxoglutarate
8.2
-
NADH + NH3 + 2-oxoglutarate
8.2
-
NAD+ + H2O + glutamate
8.3 - 8.6
-
glutamate + NAD(P)+ + H2O
8.3
-
2-oxoglutarate + NH3 + NAD(P)H
8.4 - 10
-
NADPH + 2-oxoglutarate + NH3, potassium phosphate buffer
8.5 - 8.6
-
NADPH + NH3 + 2-oxoglutarate, Tris-HCl buffer
8.5
-
NADH + 2-oxoglutarate + NH3
8.5
-
deamination, in 50 mM Tris-HCl buffer containing 3 M KCl
8.6
-
with NAD+
8.7
-
NADP+ + glutamate
8.8
-
NAD+ + glutamate
8.9
-
NAD+ + glutamate
9 - 9.5
-
glutamte deamination
9
-
homocysteinesulfinate + NAD(P)+
9
-
in the presence of 330 mM phosphate
9
-
NADH + NH3 + 2-oxoglutarate
9
-
NAD+ + glutamate
9
-
substrates: 2-oxoglutarate + NH3 + NADPH
9
-
immobilized enzyme, using NAD+ as a cofactor
9.3
-
NAD+ + glutamate
9.5 - 10
-
alpha-aminobutyrate, valine, norleucine, isoleucine, methionine or alanine + NAD(P)+
9.5
-
norvaline + NAD(P)+
9.5
-
glutamate + NADP+
9.5
-
deamination, in 50 mM CHES buffer (N-cyclohexyl-2-aminoethanesulfonic acid) containing 3 M NaCl
9.7
-
leucine + NAD(P)+
10
-
substrates: L-glutamate + H2O + NADP+
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8
-
90-100% activity
7 - 8
P49448
25-30% less active at pH 7.0 than at pH 7.5 and 8.0; equally active at pH 7.0 and 8.0
7 - 8
-
lowering the pH of the buffer from pH 8.0 to pH 7.0 increases the Km for ammonia substantially, i.e. for hGDH1 from 12.8 mM to 57.5 mM, and for hGDH2: from 14.7 mM to 62.2 mM, thus essentially precluding reductive amination
7.4 - 8.5
-
-
7.5 - 8
-
half activity of glutamate deamination compared to pH 9.5
7.5 - 8.8
-
NAD(P)H + 2-oxoglutarate + NH3, more than 50% of activity maximum at pH 7.5 and 8.8
7.75 - 8
-
maximal specific activity in TRA buffer
7.9 - 9
-
activity range, profile overview
8 - 9.2
-
deamination, more than 50% of activity maximum at pH 8.0 and 9.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
NAD+ + L-glutamate
25
-
assay at
30
P10860
assay at
35
-
NADH + NH3 + 2-oxoglutarate
37
-
assay at
37
P26443
assay at
37
-
assay at
65
-
substrates: 2-oxoglutarate + NH3 + NADPH
70
-
substrates: L-glutamate + H2O + NADP+
70
O59650
assay at
70
-
glutamate oxidation
80
O59650
oxidative deamination and reductive amination
85
-
native and recombinant enzyme
85
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 90
-
30C: about 90% of activity maximum, 90C: about 35% of activity maximum
40 - 90
O59650
40C: about 35% of maximal activity, 90C: about 75% of maximal activity, reductive amination; 40C: about 60% of maximal activity, 90C: about 85% of maximal activity, oxidative deamination
40
-
inactive at temperatures below 40C, undergoes heat activation above 40C
45 - 75
-
45C: about 35% of maximal activity, 75C: about 20% of maximal activity, substrates: 2-oxoglutarate + NH3 + NADPH
50 - 100
-
activity range, profile overview. Instability of the coenzyme at temperatures above 95C
60 - 75
-
60C: about 60% of maximal activity, 75C: about 30% of maximal activity, substrates: L-glutamate + H2O + NADP+
70 - 100
-
70C: about 35% of maximal activity, 100C: about 65% of maximal activity, reductive amination of 2-oxoglutarate
80 - 100
-
80C: about 50% of maximal activity, 100C: about 60% of maximal activity, oxidative amination of ketoglutarate
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.7
-
isoelectric focusing. Microheterogeneity shows three active bands corresponding to pI of 5.7, 5.5 and 5.4. The major band shows an isoelectric point of 5.7
8.05
P10860
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
P49448
predominantly
Manually annotated by BRENDA team
P49448
high GDH2 expression level
Manually annotated by BRENDA team
-
the enzyme is immunologically distinct from those of other mammalian brains
Manually annotated by BRENDA team
P26443
GLUD1 expression analysis
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
GLUD1 expression analysis
-
Manually annotated by BRENDA team
P49448
high expression in astrocytes, low expression in neurons
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
-
-
Manually annotated by BRENDA team
dogfish
-
-
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
-
-
Manually annotated by BRENDA team
-
glutamate dehydrogenase 1 is found only in the developing seed
Manually annotated by BRENDA team
P49448
high GDH2 expression level
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
-
-
Manually annotated by BRENDA team
P49448
mainly in Sertoli cells
Manually annotated by BRENDA team
-
from euthermic, 37C body temperature, and hibernating, 5C body temperature, animals
Manually annotated by BRENDA team
additional information
P49448
GDH2 tissue distribution, immunohistochemic analysis using a specific antibody generated with the 12-amino acid hGDH2-specific peptide PTAEFQDSISGA, corresponding to residues 436-447 of the mature human protein, overview
Manually annotated by BRENDA team
additional information
-
the enzyme occurs in state L3 and adut nematodes
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
glutamate dehydrogenase 2
Manually annotated by BRENDA team
-
almost one third of GLDH serum originates from rough endoplasmic reticulum
Manually annotated by BRENDA team
-
peripheral membrane protein
Manually annotated by BRENDA team
-
more than two third of GLDH serum originates from mitochondria
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
-
-
Manually annotated by BRENDA team
Mus musculus C57BL6/SJL hybrid
-
-
-
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1)
Thermococcus litoralis (strain ATCC 51850 / DSM 5473 / JCM 8560 / NS-C)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42000
-
SDS-PAGE
684650
61400
P10860
gel filtration
686680
160000
-
mutant enzyme H454Y, gel filtration
655569
210000
-
gel filtration
391631
240000 - 260000
-
sucrose density gradient sedimentation
391541
250000
-
liver enzyme, sedimentation velocity, light scattering
391541
250500
-
gel filtration
724653
266000 - 269000
-
gel filtration
391622
270000
-
gel filtration, sucrose density gradient centrifugation
391610
270000
-
gel filtration
391621
270000
-
gel filtration
391623
270000
-
gel filtration
391627
270000
-
recombinant enzyme, only hexameric form is enzymatically active, gel filtration
391630
270000
-
gel filtration
679617
270000
-
-
722592
284000
-
recombinant and native enzyme, gel filtration
391632
284000
O59650
gel filtration
724160
285000
-
gel filtration
391615
290000
-
hig- and low-activity form, gel filtration
391620
290000
-
gel filtration
654356
300000 - 350000
-
liver, light scattering, sedimentation equilibrium
391541
300000 - 350000
-
liver, sedimentation velocity
391541
300000 - 350000
-
liver, sedimentation equilibrium
391541
300000 - 350000
-
liver, light scattering
391541
300000 - 350000
-
liver, sedimentation equilibrium
391541
300000 - 350000
-
isoenzymes GDH1, GDH2, disc gel electrophoresis
391608
300000 - 350000
dogfish
-
liver, sedimentation equilibrium
391611
300000 - 350000
-
polyacrylamide disc gel electrophoresis
391618
320000
-
enzyme from hibernating animals, gel filtration
391636
330000
-
membrane-bound liver enzyme, velocity sedimentation on sucrose density gradient
391626
330000
-
wild-type enzyme and mutant enzymes K333L, K337L, K344L, K346L, S445L and G446L, gel filtration
655569
331000
-
gel filtration
391636
333000
-
sedimentation equilibrium
391541
333000
-
-
391606
335000
-
enzyme from euthermic animals, gel filtration
391636
336000
-
SDS-PAGE
688547
340000
-
gel filtration
391598
340000
-
gel filtration
391625
460000
-
gel filtration
655623
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 45000, SDS-PAGE
?
-
x * 57000, SDS-PAGE
?
-
x * 56000, enzymes from mitochondria and endoplasmic reticulum
?
-
x * 57500, recombinant enzyme, SDS-PAGE
?
P80053
x * 46078, calculated from sequence
?
-
x * 47122, calculated from sequence
?
Sulfolobus solfataricus MT-4
-
x * 46078, calculated from sequence
-
?
Bacillus subtilis PCI 219
-
x * 57000, SDS-PAGE
-
dimer
-
the GdhA-GdhB-Leu complex is crystallized as a heterohexamer composed of four GdhA subunits and two GdhB subunits. In this complex, six leucine molecules are bound at subunit interfaces identified as glutamate-binding sites in the GdhB-Glu complex
hexamer
-
6 * 45000, SDS-PAGE
hexamer
-
SDS-PAGE
hexamer
-
6 * 48000, SDS-PAGE
hexamer
-
6 * 48000, SDS-PAGE
hexamer
-
6 * 57000, SDS-PAGE
hexamer
-
6 * 46000, SDS-PAGE
hexamer
-
6 * 46000, SDS-PAGE
hexamer
-
6 * 54000, SDS-PAGE
hexamer
-
6 * 49000, SDS-PAGE
hexamer
-
6 * 50000, membrane-bound liver enzyme, SDS-PAGE
hexamer
-
6 * 59500, enzyme from both euthermic and hibernating animals
hexamer
-
4 * 44000 + 2 * 46000, isoenzyme GDH2, SDS-PAGE
hexamer
-
6 * 46000, recombinant enzyme, SDS-PAGE
hexamer
-
6 * 47300, recombinant enzyme, second peak in gel filtration corresponding to catalytically inactive monomer, SDS-PAGE
hexamer
-
6 * 44000, SDS-PAGE
hexamer
-
isoenzyme GDH1, SDS-PAGE
hexamer
-
6 * 53900, sedimentation equilibrium of enzyme treated with 6 M guanidinium and 0.5% 2-mercaptoethanol
hexamer
-
6 * 56000, wild-type enzyme and mutant enzymes K333L, K337L, K344L, K346L, S445L and G446L
hexamer
-
6 * 56500, hGDH1, SDS-PAGE, 6 * 56500, hGDH2, SDS-PAGE
hexamer
-
native gradient polyacryamide gel electrophoresis, 6 * 60000 Da
hexamer
-
electrostatic interactions play a key role in the relevant stability of Pyrococcus furiosus hlutamate dehydrogenase quaternary assembly at low pH although there may be other contributions involved in the complex mechanism of subunit association required for protein function
hexamer
-
6 * 40500, SDS-PAGE
hexamer
O59650
6 * 47040, calculated from sequence, the natural enzyme was purified only as a hexameric form, whereas the recombinant enzyme was purified as both monomeric and hexameric forms. Only the enzyme in a hexameric form is active. Upon heat treatment (70C for 15 min), the inactive monomeric form of the recombinant enzyme is at least partially associated with the hexameric form, 6 * 47300, SDS-PAGE, the natural enzyme was purified only as a hexameric form, whereas the recombinant enzyme was purified as both monomeric and hexameric forms. Only the enzyme in a hexameric form is active. Upon heat treatment (70C for 15 min), the inactive monomeric form of the recombinant enzyme is at least partially associated with the hexameric form
hexamer
-
the GdhB-Glu complex is a hexamer that binds 12 glutamate molecules: six molecules are bound at the substrate-binding sites, and the remaining six are bound at subunit interfaces, each composed of three subunits
homohexamer
-
-
homohexamer
-
6 * 56000, SDS-PAGE
homohexamer
P10860
method of determination not further specified
homohexamer
-
6 * 46000
octamer
-
8 * 61000, or aggregate of two tetramers, SDS-PAGE
oligomer
-
at 25C the enzyme is mostly represented by monomeric subunits at concentrations lower than 0.02 mg/ml, while oligomers are predominant at concentrations higher than 0.12 mg/ml
tetramer
-
4 * 52000, SDS-PAGE
trimer
-
6 * 56000, mutant enzyme H454Y
trimer
-
analytical ultracentrifugation
monomer
-
at 25C the enzyme is mostly represented by monomeric subunits at concentrations lower than 0.02 mg/ml, while oligomers are predominant at concentrations higher than 0.12 mg/ml
additional information
-
Thermus thermophilus, possesses GDH with a unique subunit configuration composed of two different subunits, GdhA, the regulatory subunit, and GdhB, the catalytic subunit, structure of the GdhA-GdhB-Leu complex, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
limited trypsin proteolysis removes a 39 amino acid peptide from the enzyme
additional information
-
lysine methylation not found
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapour diffusion method, structure of apoenzyme
-
hanging-drop method of vapour diffusion using lithium sulfate as the precipitant. The crystals belong to the tetragonal system and are in space group P4(2)2(1)2 with unit-cell dimensions of a = b = 167.2, c = 172.9 A. Consideration of the values of Vm and possible packing of the molecules within the cell suggest that the asymmetric unit contains a trimer
-
the crystal structure is determined at 2.2 A resolution and compared with the structure of glutamate dehydrogenase from the mesophile Clostridium symbiosum
-
hanging drop method of vapour diffusion, crystals belong to space group C2 with a hexamer in the asymmetric unit and have lattice constants a = 141.9 A, b = 197.5 A and c = 125.7 A with beta = 113.6, the crystal structure of the extremely thermostable glutamate dehydrogenase from Thermococcus litoralis determined at 2.5 A resolution is compared to that from the hyperthermophile Pyrococcus furiosus. The less stable Thermococcus litoralis enzyme has a decreased number of ion pair interactions; modified patterns of hydrogen bonding resulting from isosteric sequence changes; substitutions that decrease packing efficiency; and substitutions which give rise to subtle but distinct shifts in both main-chain and side-chain elements of the structure
Q56304
hanging-drop vapor-diffusion method at 20C, the enzyme is crystallized in the presence of both polyethylene glycol 8000 and lithium sulfate. Four types of crystals having different morphologies appeared in the crystallization trials. One type is suitable for X-ray crystal structure analysis. The crystal belongs to the monoclinic space group P2(1) and the unit-cell parameters were a = 112.99, b = 163.70, c = 133.07 A, beta = 113.46
-
the active-site cleft of unligated glutamate dehydrogenase from Thermococcus profundus studied by cryogenic X-ray crystal structure analysis and small-angle X-ray scattering
-
purified recombinant untagged GDHA and GDHB in complex with each other and leucine, and GDHB in complex with glutamate, hanging drop vapor diffusion method using 0.1 M HEPES-NaOH, pH 7.0, and 0.6 M ammonium phosphate as the reservoir solution, X-ray diffraction structure determination and analysis at 2.6 A and 2.1 A resolution, respectively, molecular replacement
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
3 - 9
-
at least 65% residual activity after 14 h
391621
4 - 7
-
the immobilized enzyme is very stable at pH 4, the enzyme activity does not decrease after 12 h at 45C at pH 4, immobilized preparations, as well as the soluble enzyme, remain fully active after 24 h of incubation at 60C and pH 7
684650
5.2 - 6.8
-
maximal stablility
678367
7 - 9
-
room temperature, 20% v/v glycerol, stable, room temperature, 1% v/v glycerol, 25% loss of activity after 48 h
391615
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0
-
complete loss of activity after 5 h, 20% glycerol protects from inactivation
391615
5
-
moderately stable above
391615
25 - 70
-
the thermostability of the enzyme at neutral pH is very high even at 70C, but at acidic pH values, the dissociation of enzyme subunits produces the rapid enzyme inactivation even at 25C, immobilized preparations, as well as the soluble enzyme, remain fully active after 24 h of incubation at 60C and pH 7, the optimal glyoxyl agarose derivative obtained is fully stable at pH 4 and 25C, retaining more than 90% of its activity after incubation at 45C for 24 h at pH 4 and more than 75% of the activity after the same period at 50C
684650
25
-
48 h, protein concentration of 0.2 mg/ml, stable
679617
37
-
complete loss of activity
391602
42
-
mitochondrial enzyme loses 80% activity after 20 min, enzyme from endoplasmic reticulum loses 20% activity
391634
45
-
half-life of hGDH1 is 310 min in absence of allosteric regulators; half-life of hGDH2 is 45 min in absence of allosteric regulators, hGDH2 is stable for 100 min in presence of 3 mM L-Leu and 1 mM ADP, mutant enzyme hGDH2 S443R has a half life of 300 min
655582
45
-
the half life of isozyme GDH1 is 310 min at 45C, the half life of isozyme GDH2 is 45 min at 45C
687565
47.5
-
GDH2 has a half-life of 38 min at 47.5C, GDH1 has a half-life of 348 min at 47.5C, high concentrations of phosphate (300 mM) have a protective effect on the thermal denaturation of both wild type hGDHs, this effect being more pronounced for GDH2
688547
55
-
short periods
391604
60
-
48 h, protein concentration of 0.2 mg/ml, 20% loss of activity
679617
66
-
10 min, 50% loss of activity
391610
70 - 100
-
no loss in activity after 1 h at 90C, 20% residual activity after 1 h at 100C
391621
74
-
10 min, complete loss of activity
391610
80
-
8 h, enzyme retains more than 95% of its activity
654356
80
-
half-life: 15 h
679617
80
-
half-life: 6 h
722322
85
-
half-life: 2 h
679617
90
-
8 h, about 35% loss of activity
654356
90
-
incubation for 1 h at 0.2 mg/ml results in 90% loss of activity, incubation for 24 h at 0.8 mg/ml results in 30% loss of activity. Inactivation is irreversible. 3 M guanidine-HCl increases the half-life of the enzyme at 90C and 0.2 mg/ml 6fold. Half-life at 90C and 0.2 mg/ml protein concentration increases more than 6fold in the presence of 0.4 M Na2SO4 and decreases 4fold in the presence of 0.4 M NaSCN
678367
90
-
half-life: 20 min
679617
90
-
half-life: 6 h
722322
95
-
half-life: 15 min at 0.4 mg/ml, 30 min at 0.8 mg/ml. Temperature-dependent inactivation of the enzyme is irreversible, this process is accompanied by a progressive increase in hydrophobic surface area which leads to protein precipitation
678367
100 - 105
-
1 mg/ml enzyme, half-life of 10.5 h at 100C, 3.5 h at 105C, and 20 h at 90C, thermal denaturation at 113C
391627
100
-
half-life: 2.3 h at 0.053 mg/ml protein concentration, 10 h at 1.06 mg/ml protein concentration
391623
100
-
native enzyme, half-life at 100C: 10.5 h, recombinant enzyme, half-life at 75C: 7h, at 90C: 8.1 h
391630
100
-
8 h, about 90% loss of activity. 6 h, about 50% loss of activity
654356
100
-
half-life: 12 h
721140
100
-
half-life: 3 h
722322
100
-
purified enzyme, 70% activity remaining after over 5 h
724653
110
-
half-life: 12.5 min
722322
110
-
thermal denaturation starts at 110C and is completed at 118C. The process of heat activation from 40 to 80C is accompanied by a much smaller increase in absorbance at 280 nm and a reversible increase in heat capacity with DELTAcal = 187 Kcal/mol GDH and Tm = 57C. This absorbance change as well as the moderate increase in heat capacity suggest that thermal activation leads to some exposure of hydrophobic groups to solvent water as the GDH structure is opened slightly. The increase in absorbance at 280 nm during activation is only 12% of that for denaturation
722592
113
-
Tm-value = 113C
722592
118
-
thermal denaturation starts at 110C and is comp1eted at 118C
722592
120
-
half-life: 2.5 min
722322
additional information
-
hGDH1: much slower heat inactivation processes in presence of 1 mM ADP or 3 mM L-Leu; much slower heat inactivation processes in presence of 1 mM ADP or 3 mM L-Leu
655582
additional information
-
Q441R or S445L mutation makes the enzyme more resistant to thermal inactivation compared to wild-type, K450E or H454Y mutation makes the enzyme extremely heat-labile compared to wild-type
699658
additional information
-
at 25C the enzyme is mostly represented by monomeric subunits at concentrations lower than 0.02 mg/ml, while oligomers are predominant at concentrations higher than 0.12 mg/ml. Only the oligomeric form is temperature resistant
718955
additional information
P80053
the occurrence of specific substitutions and a possible role for N-epsilon-methylation of lysine residues are discussed in view of current hypotheses on the molecular basis of thermal adaptation of proteins
719390
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
glycerol, 20% v/v, protects against cold inactivation
-
freeze-thawing decreases activity
-
glycerol, 5-20% v/v, stabilizes
-
2-mercaptoethanol stabilizes
-
glutathione stabilizes
-
absolutely stable at 4C or at room temperature for at least 6 months
-
AMP stabilizes
-
L-aspartate stabilizes
-
strong dependence on high salt concentrations for stability
-
guanidine-dependent inactivation of the enzyme at 20C is irreversible above 1.5 M guanidine hydrochloride
-
SDS: 0.1% v/v, no loss of activity after 12 h, 0.5%, half-life 5 h
-
urea: 4 M, 10% loss of activity after 12 h, 7.5 M, half-life 9 h
-
glyoxyl agarose-GDH immobilization is more stable than CNBr-agarose preparations or than the soluble enzyme, glyoxyl agarose derivative, prepared at 4C for 15 min, immobilizes around 50% of the enzyme, but the enzyme retains almost full activity after the immobilization
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ethanol
-
50% v/v, complete loss of activity
isopropanol
-
50% v/v, complete loss of activity
Methanol
-
50% v/v, complete loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
0C, 50 mM Na,K phosphate buffer, pH 5.5, stable
-
0C, 200 mM phosphate buffer, pH 7.4, several weeks, very little loss of activity
-
5, 28% Na2SO4 solution, several weeks, very little loss of activity
-
-15, stable for several months
dogfish
-
5C, sodium phosphate buffer pH 6.8, several months, no loss of activity
-
4C, 6 months, stable
-
-18C, several months, no loss of activity
-
-20C, 4C, 25C, 6 months, 5% loss of activity
-
-70C, stable for 6 months
-
4C, 1 mg/ml protein concentration, glutamate dehydrogenase remains stable for at least one month
-
4C, 20% loss of activity after 40 days
-
4C, more than 20 days, no loss of activity
-
25C, soluble enzyme in the presence of 25% v/v acetone at pH 7, 1 week, no loss of activity
-
suspended in ammonium sulfate, stable for months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydroxylapatite, DEAE-Toyopearl, GTP-Sepharose
-
; ammonium sulfate, DEAE-cellulose, affinity precipitation with adipo-N2,N2-dihydrazido-bis(N6-carboxymethyl-NAD+)
-
brain isoenzymes 1 and 2
-
isoenzymes, glutamate dehydrogenases 1, 2 and 3
-
2',5'-ADP Sepharose 4B column and FPLC Resource-Q column chromatography
-
2,5-ADP-Sepharose column chromatography and Resource-Q column chromatography
-
ammonium sulfate fractionation, phenyl-Sepharose column chromatography, and hydroxyapatite chromatography
-
by gel filtration
-
recombinant His-tagged wild-type and mutant GDH2 from Escherichia coli
-
recombinant wild-type GLUD1 and GLUD2 from Spodoptera frugiperda Sf21 cells by ammonim sulfate fractionation, and hydrophobic interaction and hydroxyapatite chromatography
-
to homogeneity
-
using ammonium sulphate fractionation, hydrophobic interaction (using a phenylsepharose high performance column) and hydroxyapatite chromatography
-
wild-type and Glu279 mutant enzymes
-
wild-type and mutant enzyme, Q-Sepharose, omega-aminopentyl column, GTP-agarose
-
partial
-
HitrapQ, Hitrap blue, recombinant and native enzyme
-
native and recombinant enzyme
-
DEAE-Sepharose, ATP-agarose, Resource Q
-
ammonium sulfate, phenyl Sepharose, Superdex 200, Q Sepharose
-
affinity-purified
-
heat denaturation at 70C and Ni-agarose affinity column chromatography
-
recombinant His-tagged wild-type and mutant GDHA and GDHB from Escherichia coli strain BL21-CodonPlus (DE3)-RIL by affinity chromatography and gel filtration, and of untagged proteins by heat treatment at 90C for 20 min, hydrophobic interaction and anion exchange chromatography, and gel filtration to homogeneity
-
native enzyme 22.7fold by anion exchange chromatography and gel filtration to homogeneity
-
enzyme from euthermic and hibernating animals
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli BL21 by using the pET-15b expression vector containing a T7 promoter
-
chimeric mutant enzymes expressed in Escherichia coli DE3 cells
-
coexpression of wild-type and mutant enzymes with GroES and GroEl in Escherichia coli
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21 (DE3)
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in sf21 cells
-
expressed in Sf21 cells using the baculovirus expression system
-
expression in Sf21 cells using a baculovirus expression system
-
expression in Sf9 cells using the baculovirus expression system
P49448
expression of Glu279 mutants in Escherichia coli
-
expression of His-tagged GDH2 wild-type and mutants in Escherichia coli
-
gene GLUD2, expression of 12-amino acid GDH2-specific peptide PTAEFQDSISGA, corresponding to residues 436-447 of the mature human protein, in Spodoptere frugiperda Sf21 cells using the baculovirus transfection method
P49448
mutant enzymes are expressed in Escherichia coli BL21 (DE3) cells
-
mutant proteins expressed in Escherichia coli as soluble proteins
-
recombinant expression of wild-type GLUD1 and GLUD2 in Spodoptera frugiperda Sf21 cells using the baculovirus expression system
-
wild-type and mutant enzyme, expression in Sf21 cells using a baculovirus expression system
-
wild-type enzyme hGDH2 and mutant enzymes; wild-type hGDH1
-
introducing gene Glud1 under the control of the neuron-specific enolase promoter into mouse brain
P26443
expression in Escherichia coli
-
expression in Escherichia coli
-
overexpression in Escherichia coli BL21
-
expression by in vitro transcription/translation in rabbit reticulocytes
-
expression in Escherichia coli
-
expression in Escherichia coli. The specific activity of the hexameric form of the recombinant enzyme is much lower than that of the natural enzyme. The structure of the hexameric form of the recombinant enzyme with low specific activity (Type I) is different from that of the natural enzyme with high specific activity (Type II). Upon heat treatment (80C, 15 min), the Type I structure is effectively converted to Type II structure and the specific activity of the enzyme is increased by 2.6fold
O59650
expressed in Escherichia coli BL21DE3 cells
-
expression of His-tagged wild-type and mutant GDHA and GDHB in Escherichia coli strain BL21-CodonPlus (DE3)-RIL, and of untagged proteins
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A456G
-
mutant of isoenzyme hGDH2 shows no change in heat inactivation process compared to wild-type enzyme
C119A
-
reduction in the ADP-ribosylation
C119G
-
reduction in the ADP-ribosylation
C119Y
-
reduction in the ADP-ribosylation
C274A
-
reduction in the ADP-ribosylation
C274G
-
reduction in the ADP-ribosylation
C274Y
-
reduction in the ADP-ribosylation
C323G
-
decreased turnover rate of both isoenzymes as compared to wild-type
C323L
-
decreased turnover rate of both isoenzymes as compared to wild-type
C323M
-
decreased turnover rate of both isoenzymes as compared to wild-type
C323R
-
decreased turnover rate of both isoenzymes as compared to wild-type
C323Y
-
decreased turnover rate of both isoenzymes as compared to wild-type
C59A
-
reduction in the ADP-ribosylation
C59G
-
reduction in the ADP-ribosylation
D172Y
-
ratio of turnover number to Km-value for NAD+ is 1.22fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 1.2fold lower than the wild-type value, isoenzyme hGDH1, ratio of turnover number to Km-value for NAD+ is 1.2fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 1.1fold lower than the wild-type value, reduced sensitivity to ADP activation, isoenzyme hGDH2
D185A
-
site-directed mutagenesis, the mutant shows no activation by leucine in contrast to the wild-type enzyme
E279G
-
9.8fold increase in Km-value for NAD+
E279G
-
mutant enzyme is unable to bind NAD+, no difference in sensitivity to aluminum binding between wild-type and mutant enzyme
E279L
-
14.1fold increase in Km-value for NAD+
E279M
-
14.1fold increase in Km-value for NAD+
E279R
-
10.7fold increase in Km-value for NAD+
E279Y
-
11.8fold increase in Km-value for NAD+
G446C
-
a one-month-old boy with a rare form of congenital hyperinsulinism characterised by hypoglycaemia and hyperammonaemia is described. The patient is heterozygous for a novel de novo mutation in the GLUD1 gene in exon 11 of chromosome 10, which encodes glutamate dehydrogenase (GDH). This point mutation alters the corresponding guanine-guanine-thymine (GGT) codon to thymine-guaninethymine (TGT), changing the glycine at position 446 to cysteine (Gly446Cys), which is located on the allosteric domain of the enzyme. The result confirmed the diagnosis of hyperinsulinism and hyperammonaemia syndrome. The patient is treated with diazoxide (12 mg/kg/day) and the glucose infusion is gradually decreased over four days. Blood glucose is maintained around 4 mmol/l. However, the infants ammonia level remain above 120 mmol/l
G446D
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
G456A
P49448
mutant enzyme is resistant to GTP
G456A
-
mutation renders the enzyme markedly resistant to GTP inhibition, mutation abolishes the cooperative behavior of the enzyme
G96Y
-
ratio of turnover number to Km-value for NAD+ is 1.4fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 13.5fold lower than the wild-type value, isoenzyme hGDH1, ratio of turnover number to Km-value for NAD+ is 1.4fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 14.3fold lower than the wild-type value, isoenzyme hGDH2
H454Y
-
lower basal activity but comparable maximal activity as wild-type
H454Y
-
mutation results in depolymerization of hexameric enzyme into active trimers. Mutation has no effect on expression or stability of the protein. The Km-value for NADH is 1.5fold greater than the wild-type value and the KM-value for 2-oxoglutarate is 2.5fold greater than the wild-type value. Vmax values are similar for wild-type and mutant enzyme
H454Y
-
mutation in the pivot helix, mutant shows diminished basal activity and a strongly decreased maximal activity, almost no activation by L-leucine, mutant H454Y requires higher concentrations of ADP for its activation than the wild-type, mutant shows an increased resistance to GTP inhibition, mutation makes the enzyme extremely heat-labile compared to wild-type. IC50 (GTP): 2.92
H470R
-
mutant of isoenzyme hGDH2 shows no change in heat inactivation process compared to wild-type enzyme
K118Y
-
ratio of turnover number to Km-value for NAD+ is 1.8fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 9.9fold lower than the wild-type value, isoenzyme hGDH1, ratio of turnover number to Km-value for NAD+ is 2fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 8.1fold lower than the wild-type value, isoenzyme hGDH2
K130Y
-
ratio of turnover number to Km-value for NAD+ is 26.5fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 35fold lower than the wild-type value, isoenzyme hGDH2, ratio of turnover number to Km-value for NAD+ is 41.6fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 47.3fold lower than the wild-type value, isoenzyme hGDH1
K333L
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
K337L
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
K344L
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
K346L
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
K450E
-
mutation in the pivot helix, mutant shows diminished basal activity and a strongly decreased maximal activity, no activation by L-leucine, ADP restores the decreased activity of K450E but this occurs at substantially higher concentrations compared to wild-type, mutant shows an increased resistance to GTP inhibition, mutation makes the enzyme extremely heat-labile compared to wild-type. IC50 (GTP): 180
K450G
-
mutant enzyme is unable to bind GTP, no difference in sensitivity to aluminum binding between wild-type and mutant enzyme
K94Y
-
ratio of turnover number to Km-value for NAD+ is 5.6fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 25.5fold lower than the wild-type value, isoenzyme hGDH2, ratio of turnover number to Km-value for NAD+ is 6.6fold lower than the wild-type value. Ratio of turnover number to Km-value for glutamate is 37.8fold lower than the wild-type value, isoenzyme hGDH1
L415M
-
mutant of isoenzyme hGDH2 shows no change in heat inactivation process compared to wild-type enzyme
L415M/S443R/A456G
-
triple mutant hGDH2(hGDH1390-465)hGDH2 (amino acid segment 390-465 of hGDH2 replaced by the corresponding hGDH1 segment)
M370L
-
mutation does not abolish basal activity and does not abrogate the activation of the enzyme by L-Leu
M415L
-
mutation does not abolish basal activity and does not abrogate the activation of the enzyme by L-Leu
N498S
-
mutation does not render the enzyme resistant to GTP inhibition
Q441R
-
mutation in the small helix of the antenna, basal activity increased by 2fold compared to wild-type, potentiated activation by L-leucine, Q411R substitution has little effect on the allosteric regulation of the mutant by ADP and GTP compared to wild-type, mutation makes the enzyme more resistant to thermal inactivation compared to wild-type. IC50 (GTP): 0.227
Q441R
P49448
site-directed mutagenesis, the specific antibody, generated from 12-amino acid hGDH2-specific peptide PTAEFQDSISGA, corresponding to residues 436-447 of the mature human protein, shows reduced reactivity with the enzyme mutant
R151M
-
site-directed mutagenesis, the mutant shows reduced activation by leucine compared to the wild-type enzyme
R443S
P49448
mutation abolishes basal activity and renders the enzyme dependent on ADP for function
R443S
-
mutation abolishes basal activity and totally abrogates the activation of the enzyme by L-Leu, 1-10 mM, in absence of other effectors. When ADP, 0.025-0.1 mM, is present, L-Leu (0.3-6.0 mM) activates the mutant enzyme up to 2000%. The mutant enzyme is much less sensitive to ADP than the wild-type enzyme, however at 1 mM ADP the Vmax is comparable with that of wild-type enzyme GLUD1 GDH. KM-value for 2-oxoglutarate is similar to wild-type value
R443S/G456A
-
resistant to GTP inhibition
R463A
-
stimulatory effect of ADP is eliminated
R470H
-
mutation does not render the enzyme resistant to GTP inhibition
S331T
-
mutation does not abolish basal activity and does not abrogate the activation of the enzyme by L-Leu
S443R
-
mutant of isoenzyme hGDH2 shows a dramatic increase in thermal stability from 45 min at 45C for the wild-type enzyme to 300 min for the mutant enzyme. KM-values and turnover-numbers are nearly identical to wild-type enzyme
S445A
P49448
site-directed mutagenesis, the specific antibody, generated from 12-amino acid hGDH2-specific peptide PTAEFQDSISGA, corresponding to residues 436-447 of the mature human protein, shows reduced reactivity with the enzyme mutant
S445L
-
kinetic parameters are almost identical to that of the wild-type enzyme. Subunit composition and polymerisation process are not affected by matagenesis
S445L
-
mutation in the small helix of the antenna, basal activity increased by 2fold compared to wild-type, potentiated activation by L-leucine, S445L mutant retains the regulatory properties of the wild-type concerning its activation by ADP and inhibition by GTP, mutation makes the enzyme more resistant to thermal inactivation compared to wild-type. IC50 (GTP): 0.317
S448P
-
unstable in Tris-buffer especially in the absence of allosteric activators, basal and maximal specific activity is lower than that from wild-type
S448P
-
mutation located in the junction of the antenna with the pivot helix, mutant shows reduced basal activity without significantly altering the allosteric regulation by GTP or ADP, mutant is slightly induced by L-leucine. IC50 (GTP): 0.186
Y187E
-
KM-values for NADH and 2-oxoglutareta are similar to wild-type values, about 4fold decrease of Vmax
Y187G
-
KM-values for NADH and 2-oxoglutareta are similar to wild-type values, about 4fold decrease of Vmax, no significant actication by ADP
Y187G
-
mutant enzyme is unable to bind ADP, no difference in sensitivity to aluminum binding between wild-type and mutant enzyme
Y187M
-
KM-values for NADH and 2-oxoglutareta are similar to wild-type values, about 4fold decrease of Vmax, no significant actication by ADP
Y187S
-
KM-values for NADH and 2-oxoglutareta are similar to wild-type values, about 4fold decrease of Vmax, no significant actication by ADP
Y197R
-
KM-values for NADH and 2-oxoglutareta are similar to wild-type values, about 4fold decrease of Vmax, no significant actication by ADP
A72D
-
site-directed mutagenesis, the mutant shows no activation by leucine in contrast to the wild-type enzyme
D166A
-
site-directed mutagenesis, the mutant shows reduced activation by leucine compared to the wild-type enzyme
I71T
-
site-directed mutagenesis, the mutant shows reduced activation by leucine compared to the wild-type enzyme
R134A
-
site-directed mutagenesis, the mutant shows no activation by leucine in contrast to the wild-type enzyme
Y38S
-
site-directed mutagenesis, the mutant shows reduced activation by leucine compared to the wild-type enzyme
M415L/R443S/G456A
-
triple mutant hGDH1(hGDH2390-465)hGDH1 (amino acid segment 390-465 of hGDH1 replaced by the corresponding hGDH2 segment)
additional information
-
the catalytic properties of the chimeric enzymes GDH1(GDH2390-448)GDH1 and GDH2(GDH1390-448)GDH2 are not altered compared to the wild type enzyme and show almost identical sensitivity to palmitoyl-CoA inhibitory aspects of the original wild type isozymes
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
complete loss of activity after incubation with 6 M guanidine hydrochloride or 7 M urea, no renaturation after dilution into 200 mM phosphate buffer
-
monomeric and oligomeric enzyme show distinct behaviour on guanidine hydrochloride perturbation at neutral pH. The monomer denaturation, although complex, is reversible. Two fluorescent tryptophan classes are detectable in the monomer, monitoring the independent unfolding of two regions through a multistate transition. The oligomeric protein shows a complex denaturation pattern with the tendency to aggregate irreversibly at high denaturant concentration
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
serum GLDH activity is an ideal marker of alcoholism since it is elevated in alcohol abuse but its activity declines promptly after the last alcohol intake
additional information
-
C323 plays an important role in catalysis by human GDH isozymes